EP4633674A2 - Swine influenza vaccine compositions and methods thereof - Google Patents

Swine influenza vaccine compositions and methods thereof

Info

Publication number
EP4633674A2
EP4633674A2 EP23904695.6A EP23904695A EP4633674A2 EP 4633674 A2 EP4633674 A2 EP 4633674A2 EP 23904695 A EP23904695 A EP 23904695A EP 4633674 A2 EP4633674 A2 EP 4633674A2
Authority
EP
European Patent Office
Prior art keywords
clause
sequence
combination
seq
clauses
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23904695.6A
Other languages
German (de)
French (fr)
Inventor
Diego DIEL
Gabriela Mansano do. NASCIMENTO
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cornell University
Original Assignee
Cornell University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cornell University filed Critical Cornell University
Publication of EP4633674A2 publication Critical patent/EP4633674A2/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5256—Virus expressing foreign proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552—Veterinary vaccine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/24011—Poxviridae
    • C12N2710/24211—Parapoxvirus, e.g. Orf virus
    • C12N2710/24241—Use of virus, viral particle or viral elements as a vector
    • C12N2710/24243—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
    • C12N2760/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
    • C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • Influenza A viruses are a diverse and deadly group of pathogens for swine. Current enzootic subtypes of Influenza A viruses circulating in swine include H1N1, H1N2, and H3N2.
  • H1N1 subtype known as classical H1N1 virus (cH1N1)
  • cH1N1 virus was first isolated from pigs in 1930 and predominated in North America until 1998, when a reassorted H3N2 emerged and became widespread.
  • Swine influenza is one of the major causes of acute respiratory disease outbreaks in pigs. Vaccination is the most common strategy to control influenza in swine, but due to the substantial antigenic diversity of circulating strains in different parts of the world, conventional approaches to develop efficient vaccines have reached limited success.
  • RNA-based vaccine to use in swine licensed by USDA that demonstrated similar levels of protection as a licensed whole inactivated viruses (WIV).
  • WIV whole inactivated viruses
  • human influenza vaccines are updated every year to ensure the closest match with circulating strains
  • swine influenza vaccines are outdated 85007-399822 -2- containing older strains that are no longer circulating in pigs.
  • the present disclosure provides novel sequences, vectors, and pharmaceutical compositions for the treatment of IAV in swine.
  • compositions and methods of the present disclosure provide several benefits compared to the current state of the art.
  • certain polypeptide and nucleotide sequences provided herein represent consensus sequences that provide protection against divergent influenza virus in swine.
  • certain polypeptide and nucleotide sequences provided herein represent chimeric sequences that provide protection against divergent influenza virus in swine.
  • the vectors provided herein are capable of inducing high levels of antibodies and T cell responses to IAV in swine.
  • FIGURES 1A-1F show generation of recombinant ORFV ⁇ 121 conH1.
  • FIGURE 1A shows a phylogenetic tree representing the placement of conH1 construct (red dot) relative to the HA sequences used for its design.
  • FIGURE 1B shows boxplots showing the genetic distance between the circulating strains used to design the consensus 85007-399822 -3- HA sequence (in red) and how the consensus-based HA (in yellow) for H1 subtype was able to reduce this distance.
  • FIGURE 1C shows a schematic representation of the pUC57- ORFV ⁇ 121 conH1-loxP-EGFP transfer plasmid and the ORFV genome depicting ORFV121 insertion site and flanking regions (left flanking –LF -and right flank -RF) used to generate the recombinant ORFV ⁇ 121 conH1.
  • the resulting virus genome contained the insertion of the consensus H1 and the GFP reporter gene into the ORFV121 gene locus.
  • Cre recombinase was used to remove the GFP from the 121 locus, resulting in the final recombinant ORFV ⁇ 121 conH1 depicting exclusively the consensus H1 sequence into the ORFV121 gene locus.
  • FIGURE 1D is an agarose gel demonstrating PCR amplification of ORF121 gene sequences (401 bp) on the wild-type virus and its absence on recombinant ORFV ⁇ 121 conH1.
  • FIGURE 1E is an agarose gel demonstrating PCR amplification of conH1 gene (1774 bp) from the ORFV ⁇ 121 conH1 virus and lack of it on the wild-type virus genome. The negative control on the picture comes from the respective PCR reaction using MiliQ water instead of DNA.
  • FIGURE 2A shows multi- and single-step growth curves of the recombinant ORFV ⁇ 121 conH1 compared to the wild-type virus in primary OFTu cells.
  • FIGURE 2B shows multi- and single-step growth curves of the recombinant ORFV ⁇ 121 conH1 performed in primary STu cells.
  • the virus titers were determined by the Spearman and Karber's method and and expressed as tissue culture infections dose 50 (TCID 50 ) per ml (Panel created using Biorender.com).
  • FIGURES 3A-3B show localization of heterologous conH1 protein expressed by ORFV ⁇ 121 conH1.
  • FIGURE 3A shows an immunofluorescence assay in 85007-399822 -4- permeabilized and non-permeabilized OFTu cells. Expression of conH1 (red fluorescence) by the recombinant virus in intracellular compartments (left) as well as on the cell membrane (right) at 1 MOI after 48 h of infection. Blue fluorescence indicates nuclear staining by DAPI.
  • FIGURE 3B shows expression of heterologous proteins by ORFV ⁇ 121 conH1 assessed by flow-cytometry. OFTu cells were infected with ORFV ⁇ 121 conH1 or wild-type OV IA82 as negative control. Infected cells were collected 48 hours post-infection, fixed, permeabilized or not, and stained with appropriate antibodies for flow cytometric analysis.
  • FIGURE 4A-4C show cross-reactivity between divergent porcine antisera and ORFV ⁇ 121 conH1.
  • FIGURE 4A shows the cross-reactivity between serum of pigs infected with 3 different strains of H1N1 IAV-S and conH1 expressed on the cell surface of OFTu permeabilized cells assessed by IFA. Positive cross-reactivity is shown by the green fluorescence, suggesting that the conH1 expressed by the recombinant ORFV ⁇ 121 conH1 virus was recognized by the host serum from infected animals.
  • FIGURE 4B is an informative table about the IAV-S isolates used for the cross-reactivity sera assay, including the pairwise identities.
  • FIGURE 4C shows a phylogenetic tree based on the nucleotide sequences of the HAs from these same isolates to evaluate genetic distance of with the conH1.
  • FIGURES 5A-5E show humoral response to immunization. IAV-S IgG responses induced by ORFV ⁇ 121 conH1 in OH/07 (FIG. 5A) and CA/09 (FIG. 5B) challenged pigs at DPC0 (before challenge) were assessed by whole virus ELISA using the viruses used for challenge (OH/07 and CA/09) as coating antigens.
  • FIGURE 5E shows a phylogenetic tree demonstrating the distance between the HA of the viruses used for the ELISA assays and the designed consensus (consensus_H1). Each sample was tested in duplicate wells.
  • 85007-399822 -5- Asterisk refers to the statistical significance between two animal groups. P-values: *P ⁇ 0.05, **P ⁇ 0.01, ***P ⁇ 0.001, ****P ⁇ 0.0001.
  • FIGURES 6A-6H show T-cell responses in PBMCs evaluated by FACS.
  • PBMCs isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of OH/07 were analyzed for: IFN ⁇ + T-helper/Memory cells (FIG. 6A), IFN ⁇ + CTLs cells (FIG. 6B), percentage of IL-17A+ CTLs (FIG. 6C), and IFN ⁇ + CTLs cells (FIG. 6D) .
  • PBMCs isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of CA/09 were also analyzed for same T cell populations, respectively (FIGS. 6E-6H).
  • Asterisk refers to the statistical significance between two animal groups.
  • FIGURES 7A-7D show T-cell immune response to immunization.
  • BAL MNCs cells isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of OH/07 were analyzed for: percentage of IL-17A+ T-lymphocytes (FIG. 7A) and IFN ⁇ + T-lymphocytes (FIG. 7B).
  • BAL MNCs isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of CA/09 were analyzed for the same T cell populations (FIGS. 7C and 7D).
  • Asterisk refers to the statistical significance between two animal groups.
  • FIGURES 8A-8D show T-cell immune response to immunization.
  • TBLN MNCs cells isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of OH/07 were analyzed for: percentage of IL-17A+ T-lymphocytes (FIG. 8A) and IFN ⁇ + T-lymphocytes (FIG. 8B).
  • TBLN MNCs isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of CA/09 were analyzed for the same T cell populations (FIGS. 8C and 8D).
  • Asterisk refers to the statistical significance between two animal groups.
  • FIGURES 9A-9B show viral load in nasal swabs evaluated by infectious virus titration and qRT-PCR.
  • FIGURE 9A shows viral shedding in OH/07 challenged pigs by infectious titer and genome copy numbers.
  • FIGURE 9B shows viral shedding in CA/09 challenged pigs by infectious titer and genome copy numbers.
  • 85007-399822 -6- Asterisk refers to the statistical significance between two animal groups.
  • FIGURES 10A-10D show lung lesions scores, viral infectious titer and viral load assessed in BAL and lung lysates of sham-immunized/challenged and ORFV ⁇ 121 conH1/challenged pigs on DPC6.
  • FIGURE 10A shows mean lung scores assessed on DPC6.
  • FIGURE 10B shows IAV-S viral RNA shedding in the BAL of swine determined by viral infectious titer TCID 50 ml -1 and RT-qPCR genome copy numbers.
  • FIGURE 10C shows viral infectious titer and genome copy numbers in the lungs of sham-immunized and ORFV ⁇ 121 conH1-immunized swine challenged with OH/07 on DPC6.
  • FIGURE 10D shows viral infectious titer and genome copy numbers in the lungs of sham-immunized and ORFV ⁇ 121 conH1-immunized swine challenged with CA/09 on DPC6.
  • Asterisk refers to the statistical significance between two animal groups. P-values: *P ⁇ 0.05, **P ⁇ 0.01, ***P ⁇ 0.001, ****P ⁇ 0.0001.
  • FIGURES 11A-11D show an overview of the chimeric vaccine strategy.
  • FIGURE 11A shows sequential immunization with the chimeric-HA constructs composed by exotic heads and sharing the same stalk domain belonging to the H1 subtype.
  • FIGURE 11B shows a phylogenetic tree representing the subclassification in two groups within the H1 subtype of Influenza A virus. The arrows indicate the subtypes used to design the head of the chimeric HAs.
  • FIGURE 11C is a representation of the construction of the recombinant plasmid for the generation of ORFV ⁇ 121 cH6/1 recombinant virus through homologous recombination.
  • FIGURE 11D is a representation of the construction of the recombinant plasmid for the generation of ORFV ⁇ 121 cH8/1 recombinant virus through homologous recombination.
  • FIGURES 12A-12E show expression of heterologous proteins by ORFV ⁇ 121 cH6/1 and ORFV ⁇ 121 cH8/1 recombinant viruses. Expression of chimeric HAs (red fluorescence) by the recombinant ORFV ⁇ 121 cH6/1 (FIG. 12A) and ORFV ⁇ 121 cH8/1 (FIG. 12B) viruses was assessed by IFA in permeabilized and non-permeabilized cells infected with 1 MOI (48 hours post-infection).
  • FIGURE 12C shows increasing levels of cH6/1 ( ⁇ 70 kDa) in ORFV ⁇ 121 cH6/1 infected ovine cells as detected by Western blot.
  • FIGURE 12D shows increasing levels of cH8/1 in ORFV ⁇ 121 cH8/1 infected ovine cells as detected by Western blot. Mock-infected OFTu cells were used as negative controls, while beta actin was used as loading control for the Western blot.
  • FIGURES 12E and 12F show flow cytometry data was consistent with the assays of FIGS. 12C and 12D, showing a slightly higher expression of cH6/1 (FIG. 12E) than cH8/1 (FIG.
  • FIGURES 13A-13C show characterization of ORFV ⁇ 121 cH6/1 and ORFV ⁇ 121 cH8/1-IAV-S.
  • FIGURE 13A shows an agarose gel demonstrating that a H1 stalk fragment was amplified, confirming its presence, and the lack of amplification of ORF121 gene, indicating that the recombinant ORFV ⁇ 121 cH6/1 and ORFV ⁇ 121 cH8/1 viruses were purified.
  • FIGURES 13B and 13C show growth curves comparing the replication of recombinant ORFV ⁇ 121 cH6/1 and ORFV ⁇ 121 cH8/1 viruses and the parental OV-IA82 virus at different time points in OFTu cells and in STu cells.
  • FIGURES 14A-14B show the dynamics of antibody responses to immunization. Increasing IgG responses induced by priming with ORFV ⁇ 121 cH6/1 and booster with ORFV ⁇ 121 cH8/1-IAV-S in Oh07 and Ca09 challenged pigs was assessed by whole virus ELISA for the challenge virus Oh07 (FIG. 14A) and Ca09 (FIG. 14B) at the indicated time points post-immunization.
  • FIGURES 15A-15B show humoral responses to immunization at day 35 assessed by whole virus ELISA against a panel of 10 divergent viruses. IgG antibody levels by prime with ORFV ⁇ 121cH6/1 and booster with ORFV ⁇ 121cH8/1-IAV-S in Oh07 (FIG. 15A) and Ca09 (FIG. 15B) challenged animals. P-values: * p ⁇ 0.05, ** p ⁇ 0.01, *** p ⁇ 0.001, **** p ⁇ 0.0001.
  • FIGURES 16A-16B show mucosal antibody responses to immunization were assessed in BAL by whole virus ELISA against a panel of 10 divergent viruses at D42. IgA antibody level induced by prime with ORFV ⁇ 121 cH6/1 and booster with 85007-399822 -8- ORFV ⁇ 121 cH8/1 in Oh07 (FIG. 16A) and Ca09 (FIG. 16B) challenged animals. P-values: * p ⁇ 0.05, ** p ⁇ 0.01, *** p ⁇ 0.001. [0025] FIGURES 17A-17B show shedding of IAV-S through nasal secretions. Viral shedding in Oh07 (FIG.
  • FIGURES 18A-18B show lung lesion scores and viral load in target tissues.
  • FIGURE 18A shows lungs lesions and presence of genomic RNA locally in swine challenged with Oh07.
  • FIGURE 18B shows lung lesion scores and viral load were evaluated in Ca09 challenged animals.
  • P-values * p ⁇ 0.05, ** p ⁇ 0.01.
  • FIGURES 19A-19D show images of macroscopic lesions found in lungs from vaccinated OV-cH6/1- ORFV-cH8/1 (FIG. 19A) and sham-immunized (FIG. 19B) piglets challenged with Oh07 virus strain, as well as vaccinated OV-cH6/1- ORFV-cH8/1 (FIG. 19C) and sham-immunized (FIG. 19D) piglets challenged with Ca09 virus strain. Signs of tissue consolidation can be identified by darker patchy areas, which are more noticeable sham-immunized animals. DETAILED DESCRIPTION [0028] Various embodiments of the invention are described herein as follows.
  • the various embodiments utilize one or more of the following sequences as shown in Table 1.
  • the ‘ATG’ start codon and the ‘TAA’ stop codons as described in the nucleic acid sequences of the following table can be omitted.
  • Table 1. Sequences Amino acid MDYKDDDDKKVKLVVLLYTFTAANADTICIGYHANNSTDT SI S 85007-399822 -9- TIADQRTLYQTANAYVSVGSSQYSRKFNPEIATRPKVRDQA GRMNYYWTLVEPGDTITFEATGNLIAPRYAFALKRSSGSGIII S G T Q C A G T A C A 85007-399822 -10- GGAGACACAATAACATTTGAAGCAACTGGAAATCTAATA GCACCGAGATATGCCTTCGCATTGAAAAGAAGTTCTGGA G A G C T G T G G T T G L 85007-399822 -11- ( SEQ ID NO: 3) WGVHHPGTDKDQTSLYA
  • amino acid sequence refers to a sequence of amino acids in a protein, and includes sequences of amino acids in which one or more amino acids of the sequence have had their side-groups chemically modified, as well as those in which, relative to a known sequence, one or more amino acids have been replaced, inserted or deleted, without thereby eliminating a desired property.
  • An amino acid sequence may also be referred to as a peptide, oligopeptide, or protein.
  • a consensus H1 hemagglutinin polypeptide refers to a full-length coding sequence of HA from H1 subtype. Such polypeptide can be generated in silico using analysis and alignment of a large set of isolated IAV sequences from H1 subtypes obtained from clinical diagnostic cases.
  • a consensus H3 hemagglutinin polypeptide refers to a full-length coding sequence of HA from H3 subtype. Such polypeptide can be generated in silico using analysis and alignment of a large set of isolated IAV sequences from H3 subtypes obtained from clinical diagnostic cases.
  • the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1.
  • the consensus H1 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1.
  • the consensus H1 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1.
  • the consensus H1 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide 85007-399822 -22- comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1.
  • the consensus H1 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1.
  • sequence identity and “homology” with respect to a polypeptide or amino acid sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity.
  • nucleic acid or nucleotide sequence Alignment for purposes of determining percent sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALINETM (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of sequences being compared.
  • a nucleotide sequence comprising a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide is provided.
  • nucleic acid sequences that encode all or part of a polypeptide with or without a signal sequence are provided. Typically, a nucleotide sequence encoding the polypeptide of interest is inserted into an expression vector, suitable for expression in a selected host cell.
  • the nucleic acid sequence comprises SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2.
  • the nucleic acid sequence comprises at least 95% sequence 85007-399822 -23- identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2. [0035] In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells.
  • the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1.
  • the consensus H1 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. [0037] In an illustrative aspect, a recombinant polynucleotide is provided.
  • the recombinant polynucleotide comprises a heterologous regulatory element operably linked to a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide.
  • the previously described embodiments of the consensus H1 hemagglutinin polypeptide are applicable to the recombinant polynucleotide described 85007-399822 -24- herein.
  • the previously described embodiments of the nucleic acid sequence are applicable to the recombinant polynucleotide described herein.
  • the heterologous regulatory element is a promoter that functions in prokaryotic cells.
  • regulatory element refers to a nucleic acid sequence that facilitates and/or controls gene expression and/or protein expression, either directly or indirectly.
  • a regulatory element may be a promoter, enhancer, silencer, or a nucleic acid sequence encoding a micro RNA (miRNA) or transcription factor. Regulatory elements may increase or decrease gene expression and/or protein expression.
  • a regulatory element binds regulatory proteins, such as transcription factors, to control gene expression and/or protein expression.
  • a regulatory element encodes a transcription factor that controls gene expression and/or protein expression.
  • a regulatory element encodes a miRNA that binds to a target mRNA to control protein expression.
  • the regulatory element is a controllable regulatory element.
  • the regulatory element is an uncontrollable regulatory element, such as a constitutive promoter.
  • the regulatory element is a positive regulatory element, such as a promoter.
  • the regulatory element is a negative regulatory element, such as a silencer.
  • the regulatory element provides for transient, inducible (e.g., tetracycline-responsive promoter, or hypoxia-inducible promoter), and/or tissue-specific gene expression and/or protein expression.
  • the regulatory element is operably linked to the nucleic acids encoding the polypeptides (coding sequence) of the present disclosure.
  • the regulatory element need not be contiguous with the coding sequence as long as they function to direct the expression of the encoded polypeptides. Thus, for example, intervening untranslated yet transcribed sequences may be present between a promoter sequence and a coding sequence and the promoter sequence may still be considered “operably linked” to the coding sequence.
  • the regulatory element is not operably linked to the nucleic acids encoding the polypeptides of the present disclosure.
  • the regulatory element may be a microRNA sequence or transcription factor expressed from the same vector or a different vector as the nucleic acids encoding the polypeptides.
  • a composition comprising a consensus H1 hemagglutinin polypeptide and a vector is provided.
  • the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence.
  • the amino acid sequence comprises SEQ ID NO: 1.
  • the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1.
  • the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1.
  • the amino acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1.
  • the consensus H1 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H1 hemagglutinin polypeptide.
  • the nucleic acid sequence comprises SEQ ID NO: 2.
  • the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2.
  • the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2.
  • the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2.
  • the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2.
  • the nucleic acid sequence 85007-399822 -26- comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells.
  • vector is used to describe a polynucleotide that can be engineered to contain a cloned polynucleotide or polynucleotides that can be propagated in a host cell.
  • a vector can include one or more of the following elements: an origin of replication, one or more regulatory elements (such as, for example, promoters or enhancers) that regulate the expression of the polypeptide of interest, or one or more selectable marker genes (such as, for example, antibiotic resistance genes and genes that can be used in colorimetric assays, for example, ⁇ -galactosidase).
  • expression vector refers to a vector that is used to express a polypeptide of interest in a host cell.
  • a “host cell” refers to a cell that may be or has been a recipient of a vector or isolated polynucleotide.
  • Host cells may be prokaryotic cells or eukaryotic cells.
  • Exemplary eukaryotic cells include mammalian cells, such as primate or non-primate animal cells; fungal cells, such as yeast; plant cells; and insect cells.
  • Nonlimiting exemplary mammalian cells include, but are not limited to, NS0 cells, PER.C6® cells (Crucell), 293 cells, and CHO cells, and their derivatives, such as 293-6E, DG-44, CHO- S, and CHO-K cells.
  • Host cells include progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or in genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation.
  • a host cell includes cells transfected in vivo with a polynucleotide(s) encoding an amino acid sequence(s) provided herein.
  • a vector may be a nucleic acid plasmid deliverable via non-viral methods (e.g., naked DNA/RNA, formulated DNA/RNA, or liposome), or via viral methods.
  • the vector is a viral vector, such as a retroviral vector, a herpesviral 85007-399822 -27- vector, an adenoviral vector, an adeno-associated viral vector, or a poxviral vector.
  • the vector may be a bacterial vector.
  • the vector is a viral vector.
  • the viral vector is an ORFV vector.
  • Orf virus (ORFV) is a large DNA virus that is able to harbor and efficiently deliver viral antigens to animals.
  • ORFV vector does not comprise ORFV121.
  • the vector is a nucleic acid vector.
  • the nucleic acid vector is a DNA vector. In an embodiment, the nucleic acid vector is a RNA vector.
  • a pharmaceutical composition comprises i) a consensus H1 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers.
  • the consensus H1 hemagglutinin polypeptide is comprised in the composition according to a corresponding embodiment described herein.
  • the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence. The previously described embodiments of the amino acid sequence are applicable to the pharmaceutical composition described herein.
  • the consensus H1 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H1 hemagglutinin polypeptide.
  • the previously described embodiments of the nucleic acid sequence are applicable to the pharmaceutical composition described herein.
  • a “pharmaceutically acceptable carrier” refers to a non-toxic solid, semisolid, or liquid filler, diluent, encapsulating material, formulation auxiliary, or carrier conventional in the art for use with a therapeutic agent that together comprise a “pharmaceutical composition” for administration to a subject.
  • a pharmaceutically acceptable carrier is non-toxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation.
  • the pharmaceutically acceptable carrier is appropriate for the formulation employed.
  • Examples of 85007-399822 -28- pharmaceutically acceptable carriers include alumina; aluminum stearate; lecithin; serum proteins, such as human serum albumin, canine or other animal albumin; buffers such as phosphate, citrate, tromethamine or HEPES buffers; glycine; sorbic acid; potassium sorbate; partial glyceride mixtures of saturated vegetable fatty acids; water; salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, or magnesium trisilicate; polyvinyl pyrrolidone, cellulose-based substances; polyethylene glycol; sucrose; mannitol; or amino acids including, but not limited to, arginine.
  • the pharmaceutically acceptable carrier has a pH of from about 6.2 to about 7, of from about 6 to about 7.2, of from about 6.4 to about 6.8, of about 6, or of about 7 and comprises sodium phosphate and sodium chloride. In some embodiments, the pharmaceutically acceptable carrier has a pH of from about 6.2 to about 7, of from about 6 to about 7.2, of about 6, of from about 6.4 to about 6.8, or of about 7 and comprises sodium citrate and sodium chloride. [0059] In some embodiments, the pharmaceutically acceptable carrier comprises sodium phosphate, sodium chloride, and polysorbate 80. In some embodiments, the pharmaceutically acceptable carrier comprises sodium phosphate, sodium chloride, and polysorbate 20.
  • the pharmaceutically acceptable carrier comprises sodium citrate, sodium chloride, and polysorbate 20. In some embodiments, the pharmaceutically acceptable carrier comprises sodium citrate, sodium chloride, and polysorbate 80. [0060] In some embodiments, the pharmaceutically acceptable carrier comprises sodium chloride at a concentration of from about 100 nM to about 180 nM, of from about 110 nM to about 170 nM, of from about 120 nM to about 160 nM, of from about 130 nM to about 150 nM, of about 140 nM, of from about 130 nM to about 160 nM, of from about 120 nM to about 150 nM, of about 100 nM, of about 110 nM, of about 120 nM, of about 130 nM, of about 140 nM, of about 150 nM, of about 160 nM, of about 170 nM, or of about 180 nM.
  • the pharmaceutically acceptable carrier comprises sodium phosphate at a concentration of from about 100 nM to about 180 nM, of from about 110 nM to about 170 nM, of from about 120 nM to about 160 nM, of from about 130 nM to about 150 nM, of about 140 nM, of from about 130 nM to about 160 nM, of from about 120 nM to about 150 nM, of about 100 nM, of about 110 nM, of about 120 nM, of about 130 nM, of about 140 nM, of about 150 nM, of about 160 nM, of about 170 nM, or of about 180 nM.
  • the pharmaceutically acceptable carrier comprises a polysorbate at a concentration of about 550 nM to about 750 nM, of about 570 nM to about 730 nM, of about 590 nM to about 720 nM, of about 600 nM to about 700 nM, of about, 620 nM to about 680 nM, of about 640 nM to about 660 nM, of about 650 nM, of about 570 nM to about 670 nM, of about 550 nM to about 650 nM, of about 650 nM to about 750 nM, of about 630 nm to about 700 nM, or of about 670 nM to about 600 nM.
  • the polysorbate is polysorbate 80. In some embodiments, the polysorbate is polysorbate 20.
  • the pharmaceutically acceptable carrier comprises m-cresol or benzyl alcohol. In some embodiments, the concentration of m-cresol is about 0.2%, of from about 0.1% to about 0.3%, of from about 0.08% to about 0.25%, or of from about 0.05% to about 0.25%. In some embodiments, the concentration of benzyl alcohol is about 1%, of from about 0.5% to about 2%, of from about 0.2% to about 2.5%, of about 1% to about 5%, of about 0.5% to about 5%, or of about 1% to about 3%.
  • the pharmaceutical composition can be stored in lyophilized form; thus, in some embodiments, the preparation process includes a lyophilization step.
  • the lyophilized composition is then reformulated, typically as an aqueous composition suitable for parenteral administration, prior to administration to the cat.
  • the pharmaceutical composition can be stored as a liquid, i.e., aqueous, composition, which may be administered directly, or with appropriate dilution, to the dog, cat, or horse. It can be reconstituted with sterile Water for Injection (WFI), and 85007-399822 -30- Bacteriostatic reagents such benzyl alcohol may be included.
  • WFI sterile Water for Injection
  • Bacteriostatic reagents such benzyl alcohol may be included.
  • the pharmaceutical composition is an oral formulation.
  • the oral formulation is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition.
  • the oral formulation is a suspension.
  • the oral formulation is a reconstitutable suspension.
  • the pharmaceutical composition is a parenteral formulation.
  • the parenteral formulation is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous.
  • the parenteral formulation is intravenous.
  • the parenteral formulation is intraarterial.
  • the parenteral formulation is intraperitoneal.
  • the parenteral formulation is intrathecal.
  • the parenteral formulation is intradermal.
  • the parenteral formulation is epidural.
  • the parenteral formulation is intracerebroventricular.
  • the parenteral formulation is intraurethral.
  • the parenteral formulation is intrasternal. In an embodiment, the parenteral formulation is intracranial. In an embodiment, the parenteral formulation is intratumoral. In an embodiment, the parenteral formulation is intramuscular. In an embodiment, the parenteral formulation is subcutaneous. [0067] In an embodiment, the pharmaceutical composition further comprises a second therapeutic agent. In an embodiment, the pharmaceutical composition is formulated as a vaccine. In an embodiment, the pharmaceutical composition is formulated as a single dose. In an embodiment, the pharmaceutical composition is formulated as a single unit dose. [0068] In an illustrative aspect, a method for inducing an immune response in an animal against an influenza A virus (IAV) is provided.
  • IAV influenza A virus
  • the method comprises the step of 85007-399822 -31- administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein.
  • therapeutically effective amount refers to an amount which gives the desired benefit to an animal. The amount may vary from one individual to another and will depend upon a number of factors, including the overall physical condition of the animal and the underlying cause of the condition to be treated.
  • the amount of the pharmaceutical composition used for therapy gives an acceptable rate of change and maintains desired response at a beneficial level.
  • a therapeutically effective amount of the pharmaceutical composition may be readily ascertained by one of ordinary skill in the art using publicly available materials and procedures.
  • the immune response comprises a Cytotoxic T lymphocyte (CTL) response. In an embodiment, the CTL response is an IAV-specific response.
  • CTL Cytotoxic T lymphocyte
  • the immune response comprises an IgG response. In an embodiment, the IgG response is an IAV-specific response.
  • the immune response comprises a T cell response. In an embodiment, the T cell response is an IAV-specific response. In an embodiment, the T cell response comprises CD8+ T cells.
  • the immune response comprises a T-helper/memory cell response. In an embodiment, the T-helper/memory cell response is an IAV-specific response.
  • the immune response comprises an IFN- ⁇ response.
  • the IFN- ⁇ response is an IAV-specific response.
  • the administration is a prophylactic administration to the animal.
  • the animal is a mammal.
  • the animal is a porcine.
  • the IAV is an IAV H1 subtype.
  • the IAV is an IAV H3 subtype.
  • the IAV is an IAV H1N1 subtype.
  • the IAV is an IAV H1N2 subtype.
  • the IAV is an IAV H3N2 subtype.
  • the method comprises a reduction in IAV viral load of the animal. In an embodiment, the method comprises a reduction in IAV virus shedding by the animal.
  • the administration is an oral administration. In an embodiment, the oral administration is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. In an embodiment, the oral formulation is a suspension. In an embodiment, the oral formulation is a reconstitutable suspension. [0078] In an embodiment, the administration is a parenteral administration.
  • the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous.
  • the parenteral formulation is intravenous.
  • the parenteral formulation is intraarterial.
  • the parenteral formulation is intraperitoneal.
  • the parenteral formulation is intrathecal.
  • the parenteral formulation is intradermal.
  • the parenteral formulation is epidural.
  • the parenteral formulation is intracerebroventricular.
  • the parenteral formulation is intraurethral.
  • the parenteral formulation is intrasternal. In an embodiment, the parenteral formulation is intracranial. In an embodiment, the parenteral formulation is intratumoral. In an embodiment, the parenteral formulation is intramuscular. In an embodiment, the parenteral formulation is subcutaneous. [0079] In an embodiment, the pharmaceutical composition is administered as a single dose. In an embodiment, the pharmaceutical composition is administered as a single unit dose. In an embodiment, the method further comprises administration of a second therapeutic agent to the animal. 85007-399822 -33- [0080] In an illustrative aspect, a method of preventing an influenza A virus (IAV) infection in an animal is provided.
  • IAV influenza A virus
  • the method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein.
  • the previously described embodiments of the method for inducing an immune response are applicable to the method of preventing an IAV infection described herein.
  • an amino acid sequence comprising a consensus H3 hemagglutinin polypeptide is provided.
  • the consensus H3 hemagglutinin polypeptide comprises SEQ ID NO: 3.
  • the consensus H3 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3.
  • the consensus H3 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3.
  • the consensus H3 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3.
  • a nucleotide sequence comprising a nucleic acid sequence encoding a consensus H3 hemagglutinin polypeptide is provided.
  • the nucleic acid sequence comprises SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4.
  • the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the 85007-399822 -34- nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4.
  • the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4.
  • the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells.
  • the consensus H3 hemagglutinin polypeptide comprises SEQ ID NO: 3.
  • the consensus H3 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3.
  • the consensus H3 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3.
  • the consensus H3 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3.
  • the consensus H3 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3.
  • a recombinant polynucleotide is provided.
  • the recombinant polynucleotide comprises a heterologous regulatory element operably linked to a nucleic acid sequence encoding a consensus H3 hemagglutinin polypeptide. 85007-399822 -35- [0087]
  • the previously described embodiments of the consensus H3 hemagglutinin polypeptide are applicable to the recombinant polynucleotide described herein.
  • the heterologous regulatory element is a promoter that functions in prokaryotic cells.
  • a composition comprising a consensus H3 hemagglutinin polypeptide and a vector is provided.
  • the consensus H3 hemagglutinin polypeptide comprises an amino acid sequence.
  • the amino acid sequence comprises SEQ ID NO: 3.
  • the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3.
  • the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3.
  • the amino acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3.
  • the consensus H3 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H3 hemagglutinin polypeptide.
  • the nucleic acid sequence comprises SEQ ID NO: 4.
  • the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4.
  • the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4.
  • the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ 85007-399822 -36- ID NO: 4.
  • the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4.
  • the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. [0092] In an embodiment, the vector is a viral vector. In an embodiment, the viral vector is an ORFV vector. In an embodiment, the ORFV vector does not comprise ORFV121.
  • the vector is a nucleic acid vector.
  • the nucleic acid vector is a DNA vector.
  • the nucleic acid vector is a RNA vector.
  • a pharmaceutical composition comprises i) a consensus H3 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers.
  • the consensus H3 hemagglutinin polypeptide is comprised in the composition according to a corresponding embodiment described herein.
  • the consensus H3 hemagglutinin polypeptide comprises an amino acid sequence.
  • the consensus H3 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H3 hemagglutinin polypeptide.
  • the previously described embodiments of the nucleic acid sequence are applicable to the pharmaceutical composition described herein. 85007-399822 -37-
  • the previously described embodiments related to pharmaceutical compositions are applicable to the additional pharmaceutical compositions described herein.
  • a method for inducing an immune response in an animal against an influenza A virus (IAV) is provided.
  • the method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein.
  • the previously described embodiments of the methods for inducing an immune response are applicable to the additional methods for inducing an immune response described herein.
  • a method of preventing an influenza A virus (IAV) infection in an animal is provided.
  • the method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein.
  • the previously described embodiments of the method for inducing an immune response are applicable to the method of preventing an IAV infection described herein.
  • an amino acid sequence comprising a chimeric polypeptide is provided.
  • a chimeric polypeptide can include molecules comprising a first portion of an IAV polypeptide and a second portion of an IAV polypeptide.
  • the first portion and the second portion can be derived from different IAV subtypes, for instance H1, H3, H6, H8, H14, and H15. Any such portions can be prepared from the proteins by standard biochemical methods, or by expressing a polynucleotide encoding one or more portions/fragments.
  • the first portion can comprise a stalk region of a contemporary H1 or H3 IAV strain and the second portion can comprise a head region (e.g., an exotic head region) derived from one of H6, H8, H14, and H15 subtypes.
  • the chimeric polypeptide comprise a contemporary region and a head region.
  • the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H6 85007-399822 -38- contemporary polypeptide.
  • the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H8 contemporary polypeptide.
  • the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H14 contemporary polypeptide. In an embodiment, the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H15 contemporary polypeptide.
  • the chimeric polypeptide comprises SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 5.
  • the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 5. [00106] In an embodiment, the chimeric polypeptide comprises SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 7.
  • the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 97% sequence identity to the 85007-399822 -39- sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 7.
  • the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 7. [00107] In an embodiment, the chimeric polypeptide comprises SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 9.
  • the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 9. [00108] In an embodiment, the chimeric polypeptide comprises SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 11.
  • the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, 85007-399822 -40- the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 11.
  • a nucleotide sequence comprising a nucleic acid sequence encoding a chimeric polypeptide.
  • the chimeric polypeptide comprise a contemporary region and a head region.
  • the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H6 contemporary polypeptide.
  • the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H8 contemporary polypeptide.
  • the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H14 contemporary polypeptide.
  • the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H15 contemporary polypeptide.
  • the nucleic acid sequence comprises SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 6.
  • the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 6. [00111] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises 85007-399822 -41- at least 85% sequence identity to the sequence of SEQ ID NO: 8.
  • the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 8. [00112] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 10.
  • the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 10.
  • the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 10. [00113] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 95% 85007-399822 -42- sequence identity to the sequence of SEQ ID NO: 12.
  • the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 12. [00114] In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. [00115] The previously described embodiments of the chimeric polypeptide for the amino acid sequence are applicable to the nucleotide sequence as described herein.
  • a recombinant polynucleotide comprises a heterologous regulatory element operably linked to a nucleic acid sequence encoding a chimeric polypeptide.
  • the previously described embodiments of the chimeric polypeptide for the amino acid sequence are applicable to the recombinant polynucleotide as described herein.
  • a composition comprising a chimeric polypeptide and a vector is provided. The previously described embodiments of the chimeric polypeptide for the amino acid sequence are applicable to the composition as described herein.
  • the vector is a viral vector.
  • the viral vector is an ORFV vector.
  • the ORFV vector does not comprise ORFV121.
  • the vector is a nucleic acid vector.
  • the nucleic acid vector is a DNA vector.
  • the nucleic acid vector is a RNA vector. 85007-399822 -43- [00121]
  • a pharmaceutical composition is provided.
  • the pharmaceutical composition comprises i) a chimeric polypeptide and ii) one or more pharmaceutically acceptable carriers.
  • the chimeric polypeptide is comprised in the composition of according to a corresponding embodiment described herein.
  • the previously described embodiments of the chimeric polypeptide for the amino acid sequence are applicable to the pharmaceutical composition as described herein.
  • the previously described embodiments of the nucleic acid sequence are applicable to the pharmaceutical composition as described herein.
  • the previously described embodiments related to pharmaceutical compositions are applicable to the additional pharmaceutical compositions described herein.
  • a method for inducing an immune response in an animal against an influenza A virus (IAV) is provided. The method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein.
  • a method of preventing an influenza A virus (IAV) infection in an animal comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein.
  • the previously described embodiments of the method for inducing an immune response are applicable to the method of preventing an IAV infection described herein.
  • the following numbered embodiments are contemplated and are non- limiting: 1. An amino acid sequence comprising a consensus H1 hemagglutinin polypeptide.
  • a nucleotide sequence comprising a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide. 85007-399822 -45- 12.
  • the nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2.
  • the nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2. 15.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2. 16. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2. 17. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. 18. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. 19.
  • nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 85007-399822 -46- 22.
  • nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1. 23. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. 24. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. 25.
  • a recombinant polynucleotide comprising a heterologous regulatory element operably linked to a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide.
  • nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2. 44.
  • nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2. 47.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. 48.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. 85007-399822 -49- 49.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells.
  • a composition comprising a consensus H1 hemagglutinin polypeptide and a vector.
  • 53. The composition of clause 52, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence.
  • 54. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises SEQ ID NO: 1.
  • 55. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1.
  • 56. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. 57.
  • the composition of clause 52, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H1 hemagglutinin polypeptide.
  • 64. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 2. 65.
  • composition of clause 63, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2.
  • 68. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2.
  • composition of clause 63, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2.
  • a pharmaceutical composition comprising i) a consensus H1 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers.
  • nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. 85007-399822 -54- 99.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. 101.
  • nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2.
  • nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells.
  • the parenteral formulation is intravenous.
  • the pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a single dose.
  • a method for inducing an immune response in an animal against an influenza A virus comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 80 to 125.
  • CTL Cytotoxic T lymphocyte
  • the immune response comprises an IgG response. 130.
  • the T cell response comprises CD8+ T cells. 134.
  • 170. A method of preventing an influenza A virus (IAV) infection in an animal, the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 80 to 125. 171.
  • a nucleotide sequence comprising a nucleic acid sequence encoding a consensus H3 hemagglutinin polypeptide. 214.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. 218.
  • nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 219.
  • nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. 220.
  • nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. 221.
  • nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 85007-399822 -65- 224.
  • the recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4. 246.
  • nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. 247.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. 248.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 249.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. 250.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. 85007-399822 -68- 251.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. 252.
  • a composition comprising a consensus H3 hemagglutinin polypeptide and a vector.
  • the composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 4. 267.
  • the composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 85007-399822 -70- 271.
  • the composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. 274.
  • a pharmaceutical composition comprising i) a consensus H3 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers. 85007-399822 -71- 283.
  • the pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H3 hemagglutinin polypeptide. 295.
  • nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4. 297.
  • nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. 298.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. 299.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 300.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. 85007-399822 -73- 301.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. 302.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. 303.
  • nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4.
  • nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells.
  • a method for inducing an immune response in an animal against an influenza A virus comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 282 to 327. 329.
  • CTL Cytotoxic T lymphocyte
  • any other suitable clause, or any combination of suitable clauses wherein the method further comprises administration of a second therapeutic agent to the animal.
  • a method of preventing an influenza A virus (IAV) infection in an animal comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 282 to 327. 373.
  • the amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 9. 431.
  • the amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 9. 438.
  • nucleotide sequence of clause 448, any other suitable clause, or any combination of suitable clauses wherein the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H6 contemporary polypeptide.
  • the nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 6. 455.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 6. 456.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 6. 457.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 6. 458.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 6. 459.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 6. 460.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 6. 85007-399822 -88- 461.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 6. 462.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises SEQ ID NO: 8. 463.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 8. 464.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 8. 465.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 8. 466.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 8. 467.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 8. 468.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 8. 469.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 8. 85007-399822 -89- 470.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 8. 471.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises SEQ ID NO: 10. 472.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 10. 473.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 10. 474.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 10. 475.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 10. 476.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 10. 477.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 10. 478.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 10. 85007-399822 -90- 479.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 10. 480.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises SEQ ID NO: 12. 481.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 12. 482.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 12. 483.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 12. 484.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 12. 485.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 12. 486.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 12. 487.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 12. 85007-399822 -91- 488.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 12. 489.
  • nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 490.
  • the nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 7. 85007-399822 -93- 506.
  • the nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 9. 509.
  • the nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 11. 518.
  • a recombinant polynucleotide comprising a heterologous regulatory element operably linked to a nucleic acid sequence encoding a chimeric polypeptide. 527.
  • 529 The recombinant polynucleotide of clause 527, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H8 contemporary polypeptide. 530.
  • 569. A composition comprising a chimeric polypeptide and a vector. 570. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 5. 571. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. 572.
  • the composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. 582.
  • the composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 9. 589.
  • the composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 11. 602.
  • the composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 11. 606.
  • the composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises a nucleic acid sequence encoding the chimeric polypeptide.
  • composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 6. 85007-399822 -104- 608.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 6. 609.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 6. 610.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 6. 611.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 6. 612.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 6. 613.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 6. 614.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 6. 615.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 8. 622.
  • composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 8. 624.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 10. 626.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 10. 627.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 10. 630.
  • composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 10. 631.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 10. 632.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 10. 633.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 10. 634.
  • nucleic acid sequence comprises SEQ ID NO: 12. 635.
  • nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 12. 636.
  • nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 12. 637.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 12. 85007-399822 -107- 638.
  • composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 12. 639.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 12. 641.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 12. 642.
  • composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 12. 643.
  • the composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells.
  • 644. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the vector is a viral vector. 645.
  • a pharmaceutical composition comprising i) a chimeric polypeptide and ii) one or more pharmaceutically acceptable carriers. 651.
  • the pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. 654.
  • the pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 5. 655.
  • the pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. 664.
  • the pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 9. 671.
  • the pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 9. 675.
  • the pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 11. 681.
  • the pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 11. 685.
  • the pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 6. 691.
  • the pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 6. 692.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 6. 693.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 6. 694.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 6. 85007-399822 -113- 695.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 6. 696.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 6. 697.
  • nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 6. 698.
  • nucleic acid sequence comprises SEQ ID NO: 8. 699.
  • nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 8. 700.
  • nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 8. 701.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 8. 702.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 8. 703.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 8. 85007-399822 -114- 704.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 8. 705.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 8. 706.
  • nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 8. 707.
  • nucleic acid sequence comprises SEQ ID NO: 10. 708.
  • nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 10. 709.
  • nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 10. 710.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 10. 711.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 10. 712.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 10. 85007-399822 -115- 713.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 10. 714.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 10. 715.
  • nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 10. 716.
  • nucleic acid sequence comprises SEQ ID NO: 12. 717.
  • nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 12. 718.
  • nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 12. 719.
  • nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 12. 720.
  • nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 12.
  • nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 12. 85007-399822 -116- 722.
  • nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 12. 723.
  • nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 12. 724.
  • nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 12. 725.
  • nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 726.
  • the pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 743.
  • the pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 85007-399822 -118- 744.
  • the pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a single dose. 748.
  • a method for inducing an immune response in an animal against an influenza A virus comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 650 to 748. 750.
  • CTL Cytotoxic T lymphocyte
  • the method of clause 754, any other suitable clause, or any combination of suitable clauses, wherein the T cell response comprises CD8+ T cells. 757.
  • a method of preventing an influenza A virus (IAV) infection in an animal comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 650 to 748. 794.
  • any other suitable clause, or any combination of suitable clauses, wherein the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 810.
  • EXAMPLE 1 Experimental Methods and Materials 85007-399822 -125- Cells and viruses
  • OFFTu Primary ovine fetal turbinate
  • STU swine turbinate cells
  • MDCK Madin-Darby Canine Kidney
  • ORFV strain IA82 (OV-IA82) (provided by Dr. Daniel Rock at University of Illinois at Urbana-Champaign), was used as the parental virus to construct the recombinant ORFV expressing the Influenza A virus of Swine (IAV-S) consensus H1 glycoprotein (HA). Swine influenza virus H1N1 A/Swine/OH/24366/2007 (provided by Dr.
  • H1N1 virus belonging to clade gamma
  • pandemic H1N1 A/California/04/2009 obtained from National Veterinary Services Laboratory [NVSL], Ames, Iowa
  • NVSL National Veterinary Services Laboratory
  • npdm new pandemic
  • Both H1N1 viruses were propagated in MDCK cells using DMEM containing TPCK-treated trypsin (2 ⁇ g ml -1 ) and 25 mM HEPES buffer. All the IAV-S isolates used in cross-reactivity assays were obtained from NVSL.
  • the DNA fragment containing the full-length of conH1 coding sequence under the control of the I1L promoter and Flag tag-epitope was chemically synthesized (GenScript®, Piscataway, NJ) and subcloned into the poxviral 85007-399822 -128- pUC57-ORFV ⁇ 121-loxP-EGFP transfer vector, previously described. Correct cloning of conH1 was confirmed by restriction enzyme analysis in 1% agarose gel. Table 3. Set of the 63 HA sequences used for the nucleotide alignment that resulted in the conH1 sequence listed above.
  • conH1 and absence of ORFV121 sequence in purified recombinant virus were confirmed by PCR screening.
  • Two pairs of internal primers were used for the PCR amplification of conH1, IAV-S-conH1-Fw-5’- ACTGCAAGCTTTATTTAAAAGTTGTTTGGTGAACTTAAATGGACTACAAAGAC GATGAGACAAGAAAG-3’ (SEQ ID. NO: 13) and IAV-S-conH1-Rv-5’- GAGGTGTCGACTTAAATACATATTCTACACTGTAAAGAC-3’ (SEQ ID.
  • ORFV121-int-Fw-5’- CCTCGGAAAAGAGCAGACAC-3’ SEQ ID. NO: 15
  • ORF121-int-Rv-5’- CTTCATCAGGCAGTCGTTCA-3’ SEQ ID. NO: 16
  • Insertion and integrity of full-length conH1 and identity and integrity of ORFV ⁇ 121 were further confirmed by sequencing on the Illumina Mi-Seq sequencing platform (Illumina, San Diego, CA) using Nextera XT DNA library preparation kit (Illumina, San Diego, CA).
  • conH1 by the ORFV ⁇ 121 conH1 recombinant virus in vitro was assessed by indirect immunofluorescence assay (IFA), flow cytometry (FC) and Western blot (WB), as previously described. Briefly, for the IFA and FC, the expression of the heterologous protein in vitro, was assessed in permeabilized and non-permeabilized OFTu cells infected with the ORFV ⁇ 121 conH1 recombinant virus by using an anti-Flag-tag epitope monoclonal mouse antibody (GenScript®, Piscataway, NJ).
  • IFA indirect immunofluorescence assay
  • FC flow cytometry
  • WB Western blot
  • the membrane was incubated with a monoclonal antibody against ⁇ -actin (Santa Cruz Biotechnology Inc., Santa Cruz, CA) at 1:1000 for 2 h at 37°C. After washing, the 85007-399822 -132- membrane was incubated once again with IRDye 800CW-labeled secondary antibody for 1 h at 37° C, washed, and developed by ChemiDoc MP Imaging System (Bio-Rad, Hercules, CA).
  • H1N1 antisera developed against A/Sw/CA/04/2009 (clade npdm), A/Sw/IL/00685/2005 (clade delta 2), or A/Sw/KY/02086/2008 (clade beta) strains.
  • H1N1 antisera presented hemagglutination inhibition (HI) titers of 1:80, 1:160, and 1:80 against the homologous viruses, respectively.
  • Uninfected OFTu and STu were used as controls (0 hpi).
  • Virus titers were determined on each time point using the Spearman and Karber’s method and expressed as tissue culture infectious dose 50 (TCID50) per milliliter.
  • TCID50 tissue culture infectious dose 50
  • Assessment of protection against divergent H1N1 swine influenza viruses after [00140] The immunogenicity and protective efficacy of the recombinant virus against divergent strains were assessed in pigs.
  • the viruses used for the challenge were A/Sw/OH/24366/2007 (H1N1) (OH07) and A/California/04/2009 (H1N1) (CA09) strain.
  • Animals from Group 1, 4 and 5 were sham immunized with MEM. While animals from Groups 2 and 3 were immunized with ORFV ⁇ 121 conH1. All animals were immunized on day 0 and received a booster immunization on day 21 post vaccination (DPV).
  • the pigs from Groups 2 and 5 were challenged with a virus suspension of the OH07 virus intranasal and intratracheal (1x10 7 TCID50 ml -1 /route) on 40 DPV.
  • the pigs from Groups 3 and 4 were challenged with a virus suspension of the CA09 virus (1x10 7 TCID50 ml -1 /route) intranasally and intratracheally on 40 DPV.
  • IAV-S-specific IgG immune responses elicited by immunization with ORFV ⁇ 121 conH1 were assessed by whole virus ELISA of serum and bronchoalveolar lavage, respectively.
  • a panel of 12 WIV antigens for IgG-ELISA were prepared as described previously with some modifications. Briefly, ultra-centrifugation on 30% sucrose cushion gradient of virus culture supernatant was performed using Optima-L 100K ultracentrifuge (Beckman Coulter) at 17,000 RPM for 1.5 hours. The virus pellet was resuspended in DMEM and heat inactivation of the virus was carried out using a water bath placed at 56°C for 30 min.
  • Immulon 1B ELISA plates (ThermoFisher Scientific, catalog no: 3355) were coated with 250 ng/well in 100 ⁇ L volume of concentrated and heat-inactivated panel of IAV-S virus in bicarbonate/carbonate coating buffer (15 mM sodium carbonate, 35 mM sodium bicarbonate, pH 9.6) in duplicate wells.
  • Optical density (OD) values were measured at 450 nm using a microplate reader (Tecan, Mannedorf, Switzerland). OD values for each test and control samples were normalized to the OD value of uncoated. All assay formats were pre-optimized using serum samples from animals of known serological status.
  • Virus titration [00145] Infectious IAV-S titers in the swabs and tissue samples were determined by the Spearman and Karber's method and expressed as tissue culture infections dose 50 (TCID 50 ) per ml.
  • Virus positive MDCK cells were detected by immunofluorescence assay using a 1:500 of a mouse monoclonal antibody (mAb) targeting conserved nucleoprotein (NP) of influenza virus (IAV-NP HB- 65462 mAb; kindly provided by Drs. Eric Nelson and Steve Lawson at SDSU), followed by incubation with Goat Anti-Mouse IgG Monoclonal Antibody DyLight® 488 (Bethyl Laboratories Inc., Montgomery, TX) at 1:350 as described in “Immunofluorescence” from this section.
  • the viral titer was defined as the reciprocal of the highest dilution of the virus where there was infection/replication as evidenced by presence of fluorescent foci.
  • rRT-PCR Real-time reverse transcriptase PCR
  • RNA extractions were performed at using the MagMax Core extraction kit (Thermo Fisher, Waltham, MA, USA) and the automated KingFisher Flex nucleic acid extractor (Thermo Fisher, Waltham, MA, USA) following the manufacturer’s recommendations.
  • the presence of IAV-S RNA was assessed using RNA- to- Ct 1 Step- kit (Applied Biosystems) and custom designed primers and probe (Prime- Time qPCR probe assays, Integrated DNA Technologies, USA) targeting the conserved NP gene.
  • Amplification and detection were performed using the CFX96 Touch Real-Time PCR Detection System (Bio- Rad), under following conditions: 10 min at 48oC for reverse transcription, 10 min at 95 °C for polymerase activation and 40 cycles of 15 s at 95 °C for denaturation and 60 s at 60 °C or annealing 85007-399822 -137- and extension.
  • a standard curve was established by using ten-fold serial dilutions from 10 ⁇ 1 to 10 ⁇ 8 of either OH/07 or CA/09 virus suspension containing 10 5.25 TCID50 ml -1 and 10 5.38 TCID 50 ml -1 , respectively.
  • PBMCs peripheral blood mononuclear cells
  • BAL bronchoalveolar lavage
  • TBLN tracheobronchial lymph nodes
  • ICS cytokine staining
  • protein transport inhibitor Brefeldin A (GolgiPlug) was added.
  • cells were harvested, washed, blocked with 1% normal rabbit serum, and separated into appropriate number of wells in a 96-well round bottom plate for surface and intracellular cytokine labeling. Appropriate isotype control antibodies were included as negative controls.
  • mAb monoclonal antibody
  • the cells were first labeled with purified mAb and its corresponding secondary antibody followed by blocking with 1% normal mouse serum. This step was followed by labeling with other cell markers together as a cocktail.
  • Cells were transferred to a 96-well round bottom plate, washed twice in 200 ⁇ l FACS buffer/well, and subjected to surface labeling using fluorochrome conjugated mAbs 85007-399822 -138- against indicated markers and their corresponding isotype controls at pre-titrated concentrations in 50 ⁇ l of FACS buffer for 30 min at 4 o C. Cells were then fixed using 1% paraformaldehyde at 4 o C for 30 min and resuspended in 200 ⁇ l FACS buffer. [00148] For intracellular labeling, cells were washed once and permeabilized with 1% saponin for 45 min at room temperature.
  • cells were washed with saponin wash buffer (0.1% saponin) and incubated with fluorochrome conjugated mAbs against indicated markers and their corresponding isotype controls using pre-titrated concentrations in 50 ⁇ l final volume in saponin wash containing 1% normal rabbit serum for 45 min at 4 o C.
  • Cells were washed once in saponin wash and labeled with indicated secondary antibodies for 45 min at 4 o C.
  • Cells were washed once and resuspended in 200 ⁇ l FACS buffer and transferred to FACS tubes and analyzed using a live cell gate in a BD FACS Aria II flow cytometer. For each sample, 100,000 events were acquired.
  • Cells were immunostained for T-helper/memory cells (CD3+CD4+CD8 ⁇ + ⁇ -) and cytotoxic T lymphocytes (CTLs) (CD3+CD4+CD8 ⁇ + ⁇ +) using specific immune markers, including purified or fluorochrome labeled antibodies anti-porcine CD3 (Southern biotech, AL), CD4 ⁇ (Southern biotech, AL), CD8 ⁇ (Southern biotech, AL), CD8 ⁇ chain (BD Pharmingen, CA), IFN- ⁇ and IL-17A, and their corresponding isotype controls at previously titrated and optimized concentrations.
  • H1N1 anti- A/California/04/2009
  • H1N1 anti- A/California/04/2009
  • H1N1 anti- A/California/04/2009
  • H1N1 anti- A/California/04/2009
  • H1N1 anti- A/California/04/2009
  • H1N1 anti- A/California/04/2009
  • H1N1 anti-A/swine/IL/00685/2005
  • H1N1N1N1 anti-A/swine/Kentucky/02086/2008
  • A/Swine/South Dakota/A02524887/2020 virus belongs to the U.S. H1N1 clade gamma, referred as classical swine lineage worldwide.
  • nucleotide identity between the HA of conH1 used to generate the recombinant virus and the HA of A/Swine/South Dakota/A02524887/2020 is 88.1%, and in the amino acid level, the similarity was 89.1% (Table 2).
  • these numbers show the HA of A/Swine/South Dakota/A02524887/2020 share the second highest homology with the HA of conH1, after only OH/07, with a pairwise identity of 89.2% and 89.8%, respectively (Table 2).
  • the vaccinated group showed a significantly increased total IgG levels on DPC0 against A/Swine/South Dakota/A02524887/2020 (clade gamma), A/Swine/Michigan/A02524810/2020 (clade npdm), A/Swine/Texas/A02245632/2020 (beta clade), A/Swine/Oklahoma/A02245707/2020 (clade beta), and A/Swine/Oklahoma/A02214419/2017 (clade delta 1).
  • these five viruses belong to different H1N1 clades, with amino acid homology ranging between 83 and 89% (Table 2).
  • the vaccinated group continued to present increased IgG with A/Swine/South Dakota/A02524887/2020 (clade gamma), A/Swine/Michigan/A02524810/2020 (clade npdm)., 85007-399822 -142- A/Swine/Oklahoma/A02245707/2020 (clade beta), and A/Swine/Oklahoma/A02214419/2017 (clade delta 1) whole virus antigens.
  • T-cell responses elicited by immunization with ORFV ⁇ 121 conH1 virus were assessed on peripheral blood mononuclear cells (PBMCs), and mononuclear cells from bronchoalveolar lavage (BAL) and tracheobronchial lymph nodes (TBLN) at DPC6.
  • PBMCs peripheral blood mononuclear cells
  • BAL bronchoalveolar lavage
  • TBLN tracheobronchial lymph nodes
  • the percentage of T- helper/memory cells (CD3+CD4+CD8 ⁇ + ⁇ -) secreting IFN-gamma (IFN ⁇ +) ( Figure 6A and 6E) and IL-17 (IL17+) ( Figure 6G) in PBMCs were significantly higher in the vaccinated groups.
  • IFN ⁇ + cytotoxic T lymphocytes were also enhanced in ORFV ⁇ 121 conH1-immunized groups compared to unvaccinated animals challenged with CA/09 ( Figure 6G). Differences in percentage of IL17+ CTLs were only observed between immunized animals and the respective sham-immunized/mock challenged group ( Figure 6D and 6H).
  • EXAMPLE 6 Material and Methods Cells and viruses [00160] Primary ovine fetal turbinate (OFTu), swine fetal turbinate (STu) and Madine Derby Canine Kidney (MDCK), were used for viral propagation and cell-based assays. The cells were cultured in Minimum Essential Medium (MEM), supplemented with 10% Fetal Bovine Serum (FBS, heat inactivated), 2 mM L-glutamine, and antibiotics (penicillin, streptomycin, and gentamicin). The wild-type ORFV (OV strain IA82) was provided by Dr.
  • MEM Minimum Essential Medium
  • FBS Fetal Bovine Serum
  • FBS Fetal Bovine Serum
  • antibiotics penicillin, streptomycin, and gentamicin
  • the cHAs were designed based on the stalk domain (nucleotide residue 1033 to 1698) of a contemporary H1N1 IAV-S strain [(A/swine/Minnesota/A02245569/2020 (H1N1) GenBank access MT372532], and exotic head domains selected to avoid IAV subtypes found in swine (H1 and H3) and those associated with HPAI (H5 and H7).
  • the head domain of the cHAs used in this study was based either in an avian Influenza A virus (AIV) belonging to the H6 subtype [(A/American Green-winged Teal/Ohio/18OS2656/2018(H6N1) GenBank access MN430905.1] or the H8 subtype [(A/Mallard/Ohio/18OS1248/2018(H8N4) GenBank access MN431074.1] ( Figure 11B).
  • AIV avian Influenza A virus
  • cH6/1 and cH8/1 restriction endonuclease sites required for DNA insertion into the ORFV121 locus of the ORFV genome were added, whereas HindIII and SalI were added to the N- and C-terminus of cH6/1, SpeI and SalI were added to the N- and C-terminus of cH8/1.
  • the Flag-tag epitope was added to the 3' end, and either the p116 , an early/late ORFV internal promoter, or the vaccinia virus late 85007-399822 -146- I1L promoter, were added to the 5’ end of the coding sequence of cH6/1 and cH8/1, respectively.
  • any potential transcription termination nucleotide sequences including the TTTTTNT poxviral transcription termination signal, were removed from the chimeric HA coding sequence through silent nucleotide substitutions.
  • the resulting synthesized DNA fragments were subcloned into the poxviral transfer vector pUC57- ORFV ⁇ 121 loxP-EGFP, resulting in two recombinant cassettes, pUC57-ORFV ⁇ 121 cH6/1- loxP-EGFP and pUC57-ORFV ⁇ 121 cH8/1-loxP-EGFP.
  • the presence of the chimeric HAs and the absence of the wild-type virus was confirmed by PCR amplicon electrophoresis analysis in 1% agarose gel using two pairs of primers designed for the PCR amplification of the stalk domain of H1, and an internal region of ORFV121 (401 bp), respectively.
  • the primers for the stalk domain of the chimeric-HAs were Fw-5’- ACTGCGGTACCTATTTAAAAGTTGTTTGGTGAACTTAAATGGG- CCTATTCGGGGCCATTGC-3’ (SEQ ID. NO: 17) and Rv-5’- GAGGTCTCGAGTTACTTGTCGTCATCGTCTTTG-TAGTCAATCT- GGTAGATCTTTGTTGAGTCCAGC-3’ (SEQ ID.
  • OFTu cells were infected with either ORFV ⁇ 121 cH6/1 or ORFV ⁇ 121 cH8/1-IAV-S, and assessed by indirect immunofluorescence assay (IFA), flow cytometry and Western Blot, as previously described.
  • IFA indirect immunofluorescence assay
  • the stability of both cH6/1 and cH8/1s gene inserted into the ORFV121 locus was evaluated during 10 serial passages of the respective recombinant virus in OFTu cells by assessing expression through IFA, as previously described. Immunization-Challenge study in swine.
  • Immunizations were performed by intramuscular injection of either 2 ml of a virus suspension containing 10 7.38 TCID50 ml -1 or (Groups 1 and 2) or 2 ml of MEM (Groups 3 and 4). Animals were immunized on day 0 (D0) and boosted on day 21 (D21). Two divergent viruses were selected for the challenge: Sw/OH/24366/2007 (H1N1) (Oh07) and A/California/04/2009 (H1N1) (Ca09).
  • pigs in groups 1 and 3 were challenged intranasally with a virus suspension containing 1x10 7 TCID50 ml -1 of IAV-S Oh07, while groups 2 and 4 received an intranasal challenge with 1x10 7 TCID50 ml -1 virus suspension of IAV-S CA09.
  • animals were monitored daily for clinical signs of influenza infection. Serum and whole blood samples were collected on days 0, 21, 28, and 35 post-immunization (D0, D21, D28, and D35), as well as on days 3, 5, and 7 post- challenge (DPC3, DPC5, and DPC7). Nasal swabs were collected at DPC0, DPC3, DPC5, and DPC7.
  • Immulon 1B ELISA plates (Thermo Fisher Scientific, catalog no: 3355) were coated with 500 ng/well of concentrated and heat-inactivated viruses instead of 250 ng and incubated them with the according goat anti-pig biotinylated antibody IgG or IgA (Bethyl Laboratories, catalog no: A100-104, or A100-102A, respectively, TX) at diluted at 1:2000 instead of 1:4000 in 5% non-fat milk Tris-buffered saline (PBS) with 0.05% Tween 20 detergent (PBST).
  • PBS non-fat milk Tris-buffered saline
  • PBST Tween 20 detergent
  • the serum samples were evaluated by measuring their optical density (OD) at 450 nm using a microplate reader (SYNERGY LX, BioTek, Winooski, VT, 85007-399822 -149- USA). To standardize the OD values, each test and control sample was compared to the OD value of an uncoated well. Prior to the actual testing, all assay formats were optimized using serum samples from animals with known serological status. Viral load and infectious virus in nasal secretions and tissues. [00173] Viral load in nasal secretions, bronchoalveolar lavage (BAL) and lungs was determined by real-time reverse transcriptase polymerase chain reaction (rRT-PCR).
  • Lung lysates for RNA extraction were prepared with 2 g of lung tissue of individual pigs which were homogenized in 20 mL MEM. Approximately 200 ⁇ l of the tissue homogenate supernatant were subjected to nucleic acid extraction using the MagMax Core extraction kit (Thermo Fisher, Waltham, MA, USA) and the KingFisher flex automated extraction platform as previously described. Real-time RT-PCR using Path- IDTM Multiplex One-Step RT-PCR kit (Thermo Fisher, Waltham, MA, USA), targeting the conserved matrix (M) gene (Integrated DNA Technologies; Coralville, IA, USA) were used to detect RNA from influenza A virus.
  • MagMax Core extraction kit Thermo Fisher, Waltham, MA, USA
  • M conserved matrix
  • the probe, and forward and reverse primers used were 5’-FAM-TCA GGC CCC CTC AAA GCC GA-BHQ1 -3′ (SEQ ID. NO: 19), 5′- AGA TGA GTC TTC TAA CCG AGG TCG -3′ (SEQ ID. NO: 20), and 5′- TGC AAA AAC ATC TTC AAG TCT CTG -3′ (SEQ ID. NO: 21), respectively.
  • the cycling conditions for amplification of the M gene target were 10 min at 48oC for reverse transcription, 10 min at 95oC for polymerase activation, 45 cycles of 15 s at 95oC for denaturation and 1 min at 60oC for annealing and extension, performed using the CFX96 Touch Real-Time PCR Detection System (Bio- Rad). Standard curves were established using ten-fold serial dilutions ranging from 10 ⁇ 1 to 10 ⁇ 8 of either Oh07 or Ca09 virus stocks. The genome copy numbers mL -1 (log10) of each sample was derived from the CTs obtained for the established standard curves by CFX Maestro software (Bio-Rad), as previously described.
  • Graphpad Prism software v9.0 (GraphPad Software, San Diego, CA, USA) was used for all statistical analyses. Shapiro–Wilk test was performed to verify data’s normality, followed by either t-test or unpaired t-test to compare means between the groups for either normal, or non-normal data, respectively. Tukey multiple comparison post-test was performed for pairwise comparison. P value lower than 0.05 was considered significant.
  • the flow cytometry data was acquired using the Attune NxT Flow Cytometer and analyzed with FlowJo software (FlowJo V10, Becton, Dickinson & Company; BD, Franklin Lakes, NJ, USA).
  • EXAMPLE 7 In vitro expression of the heterologous proteins by ORFV ⁇ 121cH6/1 and ORFV ⁇ 121cH8/1 viruses [00176] The expression of cH6/1 and cH8/1 by the respective recombinant viruses were verified through IFA, WB, and flow cytometry by using an anti-FLAG mAb. The red fluorescence in ORFV ⁇ 121cH6/1 ( Figure 12A) and ORFV ⁇ 121cH8/1 ( Figure 12B) infected cells was observed inside the cells (permeabilized) and on their surface (unpermeabilized).

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

The present disclosure provides novel sequences, vectors, and pharmaceutical compositions for the treatment of IAV in swine. Methods of using the novel sequences, vectors, and pharmaceutical compositions are also provided, including for induction of an immune response in animals and for prevention of an IAV infection in an animal.

Description

85007-399822 -1- SWINE INFLUENZA VACCINE COMPOSITIONS AND METHODS THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit under 35 USC § 119(e) of U.S. Provisional Application Serial No. 63/433242, filed on December 16, 2022, the entire disclosure of which is incorporated herein by reference. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY [0002] Incorporated by reference in its entirety is a computer-readable nucleotide/amino acid sequence listing submitted concurrently herewith and identified as follows: 36 kilobytes XML file named “85007_399822.xml,” created on December 15, 2023. BACKGROUND AND SUMMARY [0003] Influenza A viruses are a diverse and deadly group of pathogens for swine. Current enzootic subtypes of Influenza A viruses circulating in swine include H1N1, H1N2, and H3N2. The evolutionary history of swine influenza virus (IAV-S) reflects multiple introductions of influenza viruses into pigs from other species such as avian species and humans. For instance, the H1N1 subtype, known as classical H1N1 virus (cH1N1), was first isolated from pigs in 1930 and predominated in North America until 1998, when a reassorted H3N2 emerged and became widespread. [0004] Swine influenza is one of the major causes of acute respiratory disease outbreaks in pigs. Vaccination is the most common strategy to control influenza in swine, but due to the substantial antigenic diversity of circulating strains in different parts of the world, conventional approaches to develop efficient vaccines have reached limited success. Currently, there is just one RNA-based vaccine to use in swine licensed by USDA that demonstrated similar levels of protection as a licensed whole inactivated viruses (WIV). Notably, while human influenza vaccines are updated every year to ensure the closest match with circulating strains, swine influenza vaccines are outdated 85007-399822 -2- containing older strains that are no longer circulating in pigs. Thus, there exists an urgent need for new pharmaceutical compositions and method to combat IAV in swine. [0005] Accordingly, the present disclosure provides novel sequences, vectors, and pharmaceutical compositions for the treatment of IAV in swine. Methods of using the novel sequences, vectors, and pharmaceutical compositions are also provided, including for induction of an immune response in animals and for prevention of an IAV infection in an animal. [0006] The compositions and methods of the present disclosure provide several benefits compared to the current state of the art. First, certain polypeptide and nucleotide sequences provided herein represent consensus sequences that provide protection against divergent influenza virus in swine. Second, certain polypeptide and nucleotide sequences provided herein represent chimeric sequences that provide protection against divergent influenza virus in swine. Third, the vectors provided herein are capable of inducing high levels of antibodies and T cell responses to IAV in swine. Further, the vectors described herein are capable of providing protection against a homologous challenge, proving their versatility to control IAV in swine. [0007] Other objects, features and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. BRIEF DESCRIPTIONS OF THE DRAWINGS [0008] The detailed description particularly refers to the accompanying figures in which: [0009] FIGURES 1A-1F show generation of recombinant ORFVΔ121conH1. FIGURE 1A shows a phylogenetic tree representing the placement of conH1 construct (red dot) relative to the HA sequences used for its design. FIGURE 1B shows boxplots showing the genetic distance between the circulating strains used to design the consensus 85007-399822 -3- HA sequence (in red) and how the consensus-based HA (in yellow) for H1 subtype was able to reduce this distance. FIGURE 1C shows a schematic representation of the pUC57- ORFVΔ121conH1-loxP-EGFP transfer plasmid and the ORFV genome depicting ORFV121 insertion site and flanking regions (left flanking –LF -and right flank -RF) used to generate the recombinant ORFVΔ121conH1. Following homologous recombination, the resulting virus genome contained the insertion of the consensus H1 and the GFP reporter gene into the ORFV121 gene locus. After virus selection, Cre recombinase was used to remove the GFP from the 121 locus, resulting in the final recombinant ORFVΔ121conH1 depicting exclusively the consensus H1 sequence into the ORFV121 gene locus. FIGURE 1D is an agarose gel demonstrating PCR amplification of ORF121 gene sequences (401 bp) on the wild-type virus and its absence on recombinant ORFVΔ121conH1. FIGURE 1E is an agarose gel demonstrating PCR amplification of conH1 gene (1774 bp) from the ORFVΔ121conH1 virus and lack of it on the wild-type virus genome. The negative control on the picture comes from the respective PCR reaction using MiliQ water instead of DNA. FIGURE 1F shows a western blot assay demonstrating expression of conH1 (~70 kDa) by the recombinant ORFVΔ121conH1 in OFTu cells infected at MOI = 5 and harvested at 12, 24, 48, and 72 hpi culture in vitro. Cell lysates from non-infected OFTu cells were used as negative controls. Blot was developed with a Flag-tag epitope specific mAb (Figure 1C and panel assembly created using Biorender.com). [0010] FIGURES 2A-2B show replication kinetics of the recombinant ORFVΔ121conH1. FIGURE 2A shows multi- and single-step growth curves of the recombinant ORFVΔ121conH1 compared to the wild-type virus in primary OFTu cells. FIGURE 2B shows multi- and single-step growth curves of the recombinant ORFVΔ121conH1 performed in primary STu cells. The virus titers were determined by the Spearman and Karber's method and and expressed as tissue culture infections dose 50 (TCID50) per ml (Panel created using Biorender.com). [0011] FIGURES 3A-3B show localization of heterologous conH1 protein expressed by ORFVΔ121conH1. FIGURE 3A shows an immunofluorescence assay in 85007-399822 -4- permeabilized and non-permeabilized OFTu cells. Expression of conH1 (red fluorescence) by the recombinant virus in intracellular compartments (left) as well as on the cell membrane (right) at 1 MOI after 48 h of infection. Blue fluorescence indicates nuclear staining by DAPI. FIGURE 3B shows expression of heterologous proteins by ORFVΔ121conH1 assessed by flow-cytometry. OFTu cells were infected with ORFVΔ121conH1 or wild-type OV IA82 as negative control. Infected cells were collected 48 hours post-infection, fixed, permeabilized or not, and stained with appropriate antibodies for flow cytometric analysis. The gates indicated by rectangles gather positive stained cells (Panel assembly created using Biorender.com.) [0012] FIGURE 4A-4C show cross-reactivity between divergent porcine antisera and ORFVΔ121conH1. FIGURE 4A shows the cross-reactivity between serum of pigs infected with 3 different strains of H1N1 IAV-S and conH1 expressed on the cell surface of OFTu permeabilized cells assessed by IFA. Positive cross-reactivity is shown by the green fluorescence, suggesting that the conH1 expressed by the recombinant ORFVΔ121conH1 virus was recognized by the host serum from infected animals. FIGURE 4B is an informative table about the IAV-S isolates used for the cross-reactivity sera assay, including the pairwise identities. FIGURE 4C shows a phylogenetic tree based on the nucleotide sequences of the HAs from these same isolates to evaluate genetic distance of with the conH1. [0013] FIGURES 5A-5E show humoral response to immunization. IAV-S IgG responses induced by ORFVΔ121conH1 in OH/07 (FIG. 5A) and CA/09 (FIG. 5B) challenged pigs at DPC0 (before challenge) were assessed by whole virus ELISA using the viruses used for challenge (OH/07 and CA/09) as coating antigens. The breadth of IAV-S IgG immune response induced by ORFVΔ121conH1 at DPC0 was also explored against a panel of 10 divergent viruses by whole virus ELISA for the OH/07 (FIG. 5C) and CA/09 (FIG. 5D) challenged groups, respectively. FIGURE 5E shows a phylogenetic tree demonstrating the distance between the HA of the viruses used for the ELISA assays and the designed consensus (consensus_H1). Each sample was tested in duplicate wells. 85007-399822 -5- Asterisk refers to the statistical significance between two animal groups. P-values: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. [0014] FIGURES 6A-6H show T-cell responses in PBMCs evaluated by FACS. PBMCs isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of OH/07 were analyzed for: IFNγ+ T-helper/Memory cells (FIG. 6A), IFNγ+ CTLs cells (FIG. 6B), percentage of IL-17A+ CTLs (FIG. 6C), and IFNγ+ CTLs cells (FIG. 6D) . PBMCs isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of CA/09 were also analyzed for same T cell populations, respectively (FIGS. 6E-6H). Asterisk refers to the statistical significance between two animal groups. P-values: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. [0015] FIGURES 7A-7D show T-cell immune response to immunization. BAL MNCs cells isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of OH/07 were analyzed for: percentage of IL-17A+ T-lymphocytes (FIG. 7A) and IFNγ+ T-lymphocytes (FIG. 7B). BAL MNCs isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of CA/09 were analyzed for the same T cell populations (FIGS. 7C and 7D). Asterisk refers to the statistical significance between two animal groups. P- values: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. [0016] FIGURES 8A-8D show T-cell immune response to immunization. TBLN MNCs cells isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of OH/07 were analyzed for: percentage of IL-17A+ T-lymphocytes (FIG. 8A) and IFNγ+ T-lymphocytes (FIG. 8B). TBLN MNCs isolated from pigs at DPC6 following recall stimulation with 0.1 MOI of CA/09 were analyzed for the same T cell populations (FIGS. 8C and 8D). Asterisk refers to the statistical significance between two animal groups. P- values: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. [0017] FIGURES 9A-9B show viral load in nasal swabs evaluated by infectious virus titration and qRT-PCR. FIGURE 9A shows viral shedding in OH/07 challenged pigs by infectious titer and genome copy numbers. Similarly, FIGURE 9B shows viral shedding in CA/09 challenged pigs by infectious titer and genome copy numbers. 85007-399822 -6- Asterisk refers to the statistical significance between two animal groups. P-values: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. [0018] FIGURES 10A-10D show lung lesions scores, viral infectious titer and viral load assessed in BAL and lung lysates of sham-immunized/challenged and ORFVΔ121conH1/challenged pigs on DPC6. FIGURE 10A shows mean lung scores assessed on DPC6. FIGURE 10B shows IAV-S viral RNA shedding in the BAL of swine determined by viral infectious titer TCID50 ml -1 and RT-qPCR genome copy numbers. FIGURE 10C shows viral infectious titer and genome copy numbers in the lungs of sham-immunized and ORFVΔ121conH1-immunized swine challenged with OH/07 on DPC6. FIGURE 10D shows viral infectious titer and genome copy numbers in the lungs of sham-immunized and ORFVΔ121conH1-immunized swine challenged with CA/09 on DPC6. Asterisk refers to the statistical significance between two animal groups. P-values: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. [0019] FIGURES 11A-11D show an overview of the chimeric vaccine strategy. FIGURE 11A shows sequential immunization with the chimeric-HA constructs composed by exotic heads and sharing the same stalk domain belonging to the H1 subtype. FIGURE 11B shows a phylogenetic tree representing the subclassification in two groups within the H1 subtype of Influenza A virus. The arrows indicate the subtypes used to design the head of the chimeric HAs. FIGURE 11C is a representation of the construction of the recombinant plasmid for the generation of ORFVΔ121cH6/1 recombinant virus through homologous recombination. FIGURE 11D is a representation of the construction of the recombinant plasmid for the generation of ORFVΔ121cH8/1 recombinant virus through homologous recombination. [0020] FIGURES 12A-12E show expression of heterologous proteins by ORFVΔ121cH6/1 and ORFVΔ121cH8/1 recombinant viruses. Expression of chimeric HAs (red fluorescence) by the recombinant ORFVΔ121cH6/1 (FIG. 12A) and ORFVΔ121cH8/1 (FIG. 12B) viruses was assessed by IFA in permeabilized and non-permeabilized cells infected with 1 MOI (48 hours post-infection). FIGURE 12C shows increasing levels of cH6/1 (~70 kDa) in ORFVΔ121cH6/1 infected ovine cells as detected by Western blot. 85007-399822 -7- FIGURE 12D shows increasing levels of cH8/1 in ORFVΔ121cH8/1 infected ovine cells as detected by Western blot. Mock-infected OFTu cells were used as negative controls, while beta actin was used as loading control for the Western blot. FIGURES 12E and 12F show flow cytometry data was consistent with the assays of FIGS. 12C and 12D, showing a slightly higher expression of cH6/1 (FIG. 12E) than cH8/1 (FIG. 12F) at 72 hours post- infection. OV-IA82 infected OFTu cells were used as negative controls for the gating strategy, where the gated cells indicate the positive cell population. [0021] FIGURES 13A-13C show characterization of ORFVΔ121cH6/1 and ORFVΔ121cH8/1-IAV-S. FIGURE 13A shows an agarose gel demonstrating that a H1 stalk fragment was amplified, confirming its presence, and the lack of amplification of ORF121 gene, indicating that the recombinant ORFVΔ121cH6/1 and ORFVΔ121cH8/1 viruses were purified. FIGURES 13B and 13C show growth curves comparing the replication of recombinant ORFVΔ121cH6/1 and ORFVΔ121cH8/1 viruses and the parental OV-IA82 virus at different time points in OFTu cells and in STu cells. [0022] FIGURES 14A-14B show the dynamics of antibody responses to immunization. Increasing IgG responses induced by priming with ORFVΔ121cH6/1 and booster with ORFVΔ121cH8/1-IAV-S in Oh07 and Ca09 challenged pigs was assessed by whole virus ELISA for the challenge virus Oh07 (FIG. 14A) and Ca09 (FIG. 14B) at the indicated time points post-immunization. P-values: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. [0023] FIGURES 15A-15B show humoral responses to immunization at day 35 assessed by whole virus ELISA against a panel of 10 divergent viruses. IgG antibody levels by prime with ORFVΔ121cH6/1 and booster with ORFVΔ121cH8/1-IAV-S in Oh07 (FIG. 15A) and Ca09 (FIG. 15B) challenged animals. P-values: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. [0024] FIGURES 16A-16B show mucosal antibody responses to immunization were assessed in BAL by whole virus ELISA against a panel of 10 divergent viruses at D42. IgA antibody level induced by prime with ORFVΔ121cH6/1 and booster with 85007-399822 -8- ORFVΔ121cH8/1 in Oh07 (FIG. 16A) and Ca09 (FIG. 16B) challenged animals. P-values: * p < 0.05, ** p < 0.01, *** p < 0.001. [0025] FIGURES 17A-17B show shedding of IAV-S through nasal secretions. Viral shedding in Oh07 (FIG. 17A) challenged pigs and Ca09 (FIG. 17B) challenged pigs was determined by infectious titer (upper) and (lower) genome copy numbers. P-values: * p < 0.05, ** p < 0.01. [0026] FIGURES 18A-18B show lung lesion scores and viral load in target tissues. FIGURE 18A shows lungs lesions and presence of genomic RNA locally in swine challenged with Oh07. Similarly, FIGURE 18B shows lung lesion scores and viral load were evaluated in Ca09 challenged animals. P-values: * p < 0.05, ** p < 0.01. [0027] FIGURES 19A-19D show images of macroscopic lesions found in lungs from vaccinated OV-cH6/1- ORFV-cH8/1 (FIG. 19A) and sham-immunized (FIG. 19B) piglets challenged with Oh07 virus strain, as well as vaccinated OV-cH6/1- ORFV-cH8/1 (FIG. 19C) and sham-immunized (FIG. 19D) piglets challenged with Ca09 virus strain. Signs of tissue consolidation can be identified by darker patchy areas, which are more noticeable sham-immunized animals. DETAILED DESCRIPTION [0028] Various embodiments of the invention are described herein as follows. The various embodiments utilize one or more of the following sequences as shown in Table 1. Optionally, the ‘ATG’ start codon and the ‘TAA’ stop codons as described in the nucleic acid sequences of the following table can be omitted. Table 1. Sequences Amino acid MDYKDDDDKKVKLVVLLYTFTAANADTICIGYHANNSTDT SI S 85007-399822 -9- TIADQRTLYQTANAYVSVGSSQYSRKFNPEIATRPKVRDQA GRMNYYWTLVEPGDTITFEATGNLIAPRYAFALKRSSGSGIII S G T Q C A G T A C A 85007-399822 -10- GGAGACACAATAACATTTGAAGCAACTGGAAATCTAATA GCACCGAGATATGCCTTCGCATTGAAAAGAAGTTCTGGA G A G C T G T G G G T T G L 85007-399822 -11- (SEQ ID NO: 3) WGVHHPGTDKDQTSLYAQAAGRVIVSTKRSQQTVIPNIGSR PWVRGVSSIISIYWTIVKPGDILLINSTGNLIAPRGYFKIQSGK V Y A G C C A G A A C C 85007-399822 -12- TAAAACCGGGAGACATACTTTTGATTAACAGCACAGGGA ATCTAATTGCTCCTCGGGGTTACTTCAAAATACAAAGTGG A C T C A T T T A A G L V T 85007-399822 -13- contemporary KSAAYPVIKGTYNNTGNQPILYFWGVHHPPDTNEQNTLYGS polypeptide/ H6 GDRYVRMGTESMNFAKSPEIAARPAVKGQRGRIDYYWSVL N E Y E T C T C T G A A C 85007-399822 -14- GTTTTAAAACCAGGAGAGACCTTGAATGTCGAATCCAAT GGAAATCTAATTGCCCCTTGGTATGCATACAAATTTGTCA T G A G T G T G G G P 85007-399822 -15- Chimeric H1 AASYKRIRLFDYSRWNVTSSGTSKACNASTGGQSFYRSINW hemagglutinin LTKKKPDTYDFNEGSYINNEDGDIIFLWGIHHPPNTKEQTTL G C E Y E T G A G A C A A 85007-399822 -16- AGTCAGAGGACAACAAGGAAGAATGGATTACTATTGGGG CATCCTGAAAAGAGGAGAGACTCTGAAGATCAGGACCAA G A T G T T G A G T G T G G G 85007-399822 -17- Chimeric H3 NGALGSPGCDHLQDSTWDVFIERPTAVDTCYPFDVPDYQSL hemagglutinin RSILASSGSLEFIAEQFTWNGVKADGSSSACLRGGRNSFFTR N Y S T S S R S A C A T A A G A 85007-399822 -18- CCGCTCAGATCAAATCAGCATTATTCCCAACATAGGAAG TAGACCAAGAGTGAGGAACCAGAGCGGCAGAATAAGCA T G C A T A T A C T G G T G 85007-399822 -19- Amino acid MNTQIIAILALGLSVVKSDKICLGHHAVANGTKVNTLTEKG sequence – VEVVNATETVETTSINKVCTKGRKAVDLGFCGILGTIIGPPQ N G Q L F I TI C I T A A A A T A 85007-399822 -20- TTCTTTGGAGGAGCAAAACCAGCTATATGGAACTGGGAA TAAGCTGATAACAGTAGGGAGCTCAAAGTACCAACAATC G C C T T G T G A T G C T T 85007-399822 -21- AAGGCAACATTAGGTGCAACATTTGCATTTACCCATACG ATGTTCCAGATTACGCTTGA , s H1 hemagglutinin polypeptide is provided. “Amino acid sequence” refers to a sequence of amino acids in a protein, and includes sequences of amino acids in which one or more amino acids of the sequence have had their side-groups chemically modified, as well as those in which, relative to a known sequence, one or more amino acids have been replaced, inserted or deleted, without thereby eliminating a desired property. An amino acid sequence may also be referred to as a peptide, oligopeptide, or protein. [0030] A consensus H1 hemagglutinin polypeptide refers to a full-length coding sequence of HA from H1 subtype. Such polypeptide can be generated in silico using analysis and alignment of a large set of isolated IAV sequences from H1 subtypes obtained from clinical diagnostic cases. Likewise, a consensus H3 hemagglutinin polypeptide refers to a full-length coding sequence of HA from H3 subtype. Such polypeptide can be generated in silico using analysis and alignment of a large set of isolated IAV sequences from H3 subtypes obtained from clinical diagnostic cases. [0031] In an embodiment, the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide 85007-399822 -22- comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. [0032] In any embodiment described herein related to a sequence listing, the phrase “comprising” can be replaced with the phrase “consists of” or “consisting of” according to well established principles. As used herein, “sequence identity” and “homology” with respect to a polypeptide or amino acid sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. The same concepts apply with respect to a nucleic acid or nucleotide sequence. Alignment for purposes of determining percent sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALINE™ (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of sequences being compared. [0033] In an illustrative aspect, a nucleotide sequence comprising a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide is provided. Nucleotide sequences that encode all or part of a polypeptide with or without a signal sequence are provided. Typically, a nucleotide sequence encoding the polypeptide of interest is inserted into an expression vector, suitable for expression in a selected host cell. [0034] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 95% sequence 85007-399822 -23- identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2. [0035] In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. [0036] In an embodiment, the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the consensus H1 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. [0037] In an illustrative aspect, a recombinant polynucleotide is provided. The recombinant polynucleotide comprises a heterologous regulatory element operably linked to a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide. [0038] The previously described embodiments of the consensus H1 hemagglutinin polypeptide are applicable to the recombinant polynucleotide described 85007-399822 -24- herein. The previously described embodiments of the nucleic acid sequence are applicable to the recombinant polynucleotide described herein. In an embodiment, the heterologous regulatory element is a promoter that functions in prokaryotic cells. [0039] The term “regulatory element” (also referred to as a “regulatory region” or “regulatory sequence”) refers to a nucleic acid sequence that facilitates and/or controls gene expression and/or protein expression, either directly or indirectly. A regulatory element may be a promoter, enhancer, silencer, or a nucleic acid sequence encoding a micro RNA (miRNA) or transcription factor. Regulatory elements may increase or decrease gene expression and/or protein expression. [0040] In some embodiments, a regulatory element binds regulatory proteins, such as transcription factors, to control gene expression and/or protein expression. In some embodiments, a regulatory element encodes a transcription factor that controls gene expression and/or protein expression. In some embodiments, a regulatory element encodes a miRNA that binds to a target mRNA to control protein expression. [0041] In some embodiments, the regulatory element is a controllable regulatory element. In some embodiments, the regulatory element is an uncontrollable regulatory element, such as a constitutive promoter. In some embodiments, the regulatory element is a positive regulatory element, such as a promoter. In some embodiments, the regulatory element is a negative regulatory element, such as a silencer. In some embodiments, the regulatory element provides for transient, inducible (e.g., tetracycline-responsive promoter, or hypoxia-inducible promoter), and/or tissue-specific gene expression and/or protein expression. [0042] In some embodiments, the regulatory element is operably linked to the nucleic acids encoding the polypeptides (coding sequence) of the present disclosure. The regulatory element need not be contiguous with the coding sequence as long as they function to direct the expression of the encoded polypeptides. Thus, for example, intervening untranslated yet transcribed sequences may be present between a promoter sequence and a coding sequence and the promoter sequence may still be considered “operably linked” to the coding sequence. 85007-399822 -25- [0043] In some embodiments, the regulatory element is not operably linked to the nucleic acids encoding the polypeptides of the present disclosure. For example, the regulatory element may be a microRNA sequence or transcription factor expressed from the same vector or a different vector as the nucleic acids encoding the polypeptides. [0044] In an illustrative aspect, a composition comprising a consensus H1 hemagglutinin polypeptide and a vector is provided. [0045] In an embodiment, the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence. In an embodiment, the amino acid sequence comprises SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. [0046] In an embodiment, the consensus H1 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H1 hemagglutinin polypeptide. In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence 85007-399822 -26- comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2. In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. [0047] The term “vector” is used to describe a polynucleotide that can be engineered to contain a cloned polynucleotide or polynucleotides that can be propagated in a host cell. A vector can include one or more of the following elements: an origin of replication, one or more regulatory elements (such as, for example, promoters or enhancers) that regulate the expression of the polypeptide of interest, or one or more selectable marker genes (such as, for example, antibiotic resistance genes and genes that can be used in colorimetric assays, for example, β-galactosidase). The term “expression vector” refers to a vector that is used to express a polypeptide of interest in a host cell. [0048] A “host cell” refers to a cell that may be or has been a recipient of a vector or isolated polynucleotide. Host cells may be prokaryotic cells or eukaryotic cells. Exemplary eukaryotic cells include mammalian cells, such as primate or non-primate animal cells; fungal cells, such as yeast; plant cells; and insect cells. Nonlimiting exemplary mammalian cells include, but are not limited to, NS0 cells, PER.C6® cells (Crucell), 293 cells, and CHO cells, and their derivatives, such as 293-6E, DG-44, CHO- S, and CHO-K cells. Host cells include progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or in genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. A host cell includes cells transfected in vivo with a polynucleotide(s) encoding an amino acid sequence(s) provided herein. [0049] A vector may be a nucleic acid plasmid deliverable via non-viral methods (e.g., naked DNA/RNA, formulated DNA/RNA, or liposome), or via viral methods. In some embodiments, the vector is a viral vector, such as a retroviral vector, a herpesviral 85007-399822 -27- vector, an adenoviral vector, an adeno-associated viral vector, or a poxviral vector. The vector may be a bacterial vector. [0050] In an embodiment, the vector is a viral vector. In an embodiment, the viral vector is an ORFV vector. Orf virus (ORFV) is a large DNA virus that is able to harbor and efficiently deliver viral antigens to animals. [0051] In an embodiment, the ORFV vector does not comprise ORFV121. [0052] In an embodiment, the vector is a nucleic acid vector. In an embodiment, the nucleic acid vector is a DNA vector. In an embodiment, the nucleic acid vector is a RNA vector. [0053] In an illustrative aspect, a pharmaceutical composition is provided. The pharmaceutical composition comprises i) a consensus H1 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers. [0054] In an embodiment, the consensus H1 hemagglutinin polypeptide is comprised in the composition according to a corresponding embodiment described herein. [0055] In an embodiment, the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence. The previously described embodiments of the amino acid sequence are applicable to the pharmaceutical composition described herein. [0056] In an embodiment, the consensus H1 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H1 hemagglutinin polypeptide. The previously described embodiments of the nucleic acid sequence are applicable to the pharmaceutical composition described herein. [0057] A “pharmaceutically acceptable carrier” refers to a non-toxic solid, semisolid, or liquid filler, diluent, encapsulating material, formulation auxiliary, or carrier conventional in the art for use with a therapeutic agent that together comprise a “pharmaceutical composition” for administration to a subject. A pharmaceutically acceptable carrier is non-toxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation. The pharmaceutically acceptable carrier is appropriate for the formulation employed. Examples of 85007-399822 -28- pharmaceutically acceptable carriers include alumina; aluminum stearate; lecithin; serum proteins, such as human serum albumin, canine or other animal albumin; buffers such as phosphate, citrate, tromethamine or HEPES buffers; glycine; sorbic acid; potassium sorbate; partial glyceride mixtures of saturated vegetable fatty acids; water; salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, or magnesium trisilicate; polyvinyl pyrrolidone, cellulose-based substances; polyethylene glycol; sucrose; mannitol; or amino acids including, but not limited to, arginine. [0058] In some embodiments, the pharmaceutically acceptable carrier has a pH of from about 6.2 to about 7, of from about 6 to about 7.2, of from about 6.4 to about 6.8, of about 6, or of about 7 and comprises sodium phosphate and sodium chloride. In some embodiments, the pharmaceutically acceptable carrier has a pH of from about 6.2 to about 7, of from about 6 to about 7.2, of about 6, of from about 6.4 to about 6.8, or of about 7 and comprises sodium citrate and sodium chloride. [0059] In some embodiments, the pharmaceutically acceptable carrier comprises sodium phosphate, sodium chloride, and polysorbate 80. In some embodiments, the pharmaceutically acceptable carrier comprises sodium phosphate, sodium chloride, and polysorbate 20. In some embodiments, the pharmaceutically acceptable carrier comprises sodium citrate, sodium chloride, and polysorbate 20. In some embodiments, the pharmaceutically acceptable carrier comprises sodium citrate, sodium chloride, and polysorbate 80. [0060] In some embodiments, the pharmaceutically acceptable carrier comprises sodium chloride at a concentration of from about 100 nM to about 180 nM, of from about 110 nM to about 170 nM, of from about 120 nM to about 160 nM, of from about 130 nM to about 150 nM, of about 140 nM, of from about 130 nM to about 160 nM, of from about 120 nM to about 150 nM, of about 100 nM, of about 110 nM, of about 120 nM, of about 130 nM, of about 140 nM, of about 150 nM, of about 160 nM, of about 170 nM, or of about 180 nM. 85007-399822 -29- [0061] In some embodiments, the pharmaceutically acceptable carrier comprises sodium phosphate at a concentration of from about 100 nM to about 180 nM, of from about 110 nM to about 170 nM, of from about 120 nM to about 160 nM, of from about 130 nM to about 150 nM, of about 140 nM, of from about 130 nM to about 160 nM, of from about 120 nM to about 150 nM, of about 100 nM, of about 110 nM, of about 120 nM, of about 130 nM, of about 140 nM, of about 150 nM, of about 160 nM, of about 170 nM, or of about 180 nM. [0062] In some embodiments, the pharmaceutically acceptable carrier comprises a polysorbate at a concentration of about 550 nM to about 750 nM, of about 570 nM to about 730 nM, of about 590 nM to about 720 nM, of about 600 nM to about 700 nM, of about, 620 nM to about 680 nM, of about 640 nM to about 660 nM, of about 650 nM, of about 570 nM to about 670 nM, of about 550 nM to about 650 nM, of about 650 nM to about 750 nM, of about 630 nm to about 700 nM, or of about 670 nM to about 600 nM. In some embodiments, the polysorbate is polysorbate 80. In some embodiments, the polysorbate is polysorbate 20. [0063] In some embodiments, the pharmaceutically acceptable carrier comprises m-cresol or benzyl alcohol. In some embodiments, the concentration of m-cresol is about 0.2%, of from about 0.1% to about 0.3%, of from about 0.08% to about 0.25%, or of from about 0.05% to about 0.25%. In some embodiments, the concentration of benzyl alcohol is about 1%, of from about 0.5% to about 2%, of from about 0.2% to about 2.5%, of about 1% to about 5%, of about 0.5% to about 5%, or of about 1% to about 3%. [0064] The pharmaceutical composition can be stored in lyophilized form; thus, in some embodiments, the preparation process includes a lyophilization step. The lyophilized composition is then reformulated, typically as an aqueous composition suitable for parenteral administration, prior to administration to the cat. In other embodiments, particularly where the protein is highly stable to thermal and oxidative denaturation, the pharmaceutical composition can be stored as a liquid, i.e., aqueous, composition, which may be administered directly, or with appropriate dilution, to the dog, cat, or horse. It can be reconstituted with sterile Water for Injection (WFI), and 85007-399822 -30- Bacteriostatic reagents such benzyl alcohol may be included. Thus, the invention provides pharmaceutical compositions in both solid and liquid form. [0065] In an embodiment, the pharmaceutical composition is an oral formulation. In an embodiment, the oral formulation is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. In an embodiment, the oral formulation is a suspension. In an embodiment, the oral formulation is a reconstitutable suspension. [0066] In an embodiment, the pharmaceutical composition is a parenteral formulation. In an embodiment, the parenteral formulation is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. In an embodiment, the parenteral formulation is intravenous. In an embodiment, the parenteral formulation is intraarterial. In an embodiment, the parenteral formulation is intraperitoneal. In an embodiment, the parenteral formulation is intrathecal. In an embodiment, the parenteral formulation is intradermal. In an embodiment, the parenteral formulation is epidural. In an embodiment, the parenteral formulation is intracerebroventricular. In an embodiment, the parenteral formulation is intraurethral. In an embodiment, the parenteral formulation is intrasternal. In an embodiment, the parenteral formulation is intracranial. In an embodiment, the parenteral formulation is intratumoral. In an embodiment, the parenteral formulation is intramuscular. In an embodiment, the parenteral formulation is subcutaneous. [0067] In an embodiment, the pharmaceutical composition further comprises a second therapeutic agent. In an embodiment, the pharmaceutical composition is formulated as a vaccine. In an embodiment, the pharmaceutical composition is formulated as a single dose. In an embodiment, the pharmaceutical composition is formulated as a single unit dose. [0068] In an illustrative aspect, a method for inducing an immune response in an animal against an influenza A virus (IAV) is provided. The method comprises the step of 85007-399822 -31- administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein. As used herein, and when contemplating the pharmaceutical composition, the term “therapeutically effective amount” refers to an amount which gives the desired benefit to an animal. The amount may vary from one individual to another and will depend upon a number of factors, including the overall physical condition of the animal and the underlying cause of the condition to be treated. The amount of the pharmaceutical composition used for therapy gives an acceptable rate of change and maintains desired response at a beneficial level. A therapeutically effective amount of the pharmaceutical composition may be readily ascertained by one of ordinary skill in the art using publicly available materials and procedures. [0069] In an embodiment, the immune response comprises a Cytotoxic T lymphocyte (CTL) response. In an embodiment, the CTL response is an IAV-specific response. [0070] In an embodiment, the immune response comprises an IgG response. In an embodiment, the IgG response is an IAV-specific response. [0071] In an embodiment, the immune response comprises a T cell response. In an embodiment, the T cell response is an IAV-specific response. In an embodiment, the T cell response comprises CD8+ T cells. [0072] In an embodiment, the immune response comprises a T-helper/memory cell response. In an embodiment, the T-helper/memory cell response is an IAV-specific response. [0073] In an embodiment, the immune response comprises an IFN-γ response. In an embodiment, the IFN-γ response is an IAV-specific response. [0074] In an embodiment, the administration is a prophylactic administration to the animal. In an embodiment, the animal is a mammal. In an embodiment, the animal is a porcine. [0075] In an embodiment, the IAV is an IAV H1 subtype. In an embodiment, the IAV is an IAV H3 subtype. In an embodiment, the IAV is an IAV H1N1 subtype. In an 85007-399822 -32- embodiment, the IAV is an IAV H1N2 subtype. In an embodiment, the IAV is an IAV H3N2 subtype. [0076] In an embodiment, the method comprises a reduction in IAV viral load of the animal. In an embodiment, the method comprises a reduction in IAV virus shedding by the animal. [0077] In an embodiment, the administration is an oral administration. In an embodiment, the oral administration is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. In an embodiment, the oral formulation is a suspension. In an embodiment, the oral formulation is a reconstitutable suspension. [0078] In an embodiment, the administration is a parenteral administration. In an embodiment, the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. In an embodiment, the parenteral formulation is intravenous. In an embodiment, the parenteral formulation is intraarterial. In an embodiment, the parenteral formulation is intraperitoneal. In an embodiment, the parenteral formulation is intrathecal. In an embodiment, the parenteral formulation is intradermal. In an embodiment, the parenteral formulation is epidural. In an embodiment, the parenteral formulation is intracerebroventricular. In an embodiment, the parenteral formulation is intraurethral. In an embodiment, the parenteral formulation is intrasternal. In an embodiment, the parenteral formulation is intracranial. In an embodiment, the parenteral formulation is intratumoral. In an embodiment, the parenteral formulation is intramuscular. In an embodiment, the parenteral formulation is subcutaneous. [0079] In an embodiment, the pharmaceutical composition is administered as a single dose. In an embodiment, the pharmaceutical composition is administered as a single unit dose. In an embodiment, the method further comprises administration of a second therapeutic agent to the animal. 85007-399822 -33- [0080] In an illustrative aspect, a method of preventing an influenza A virus (IAV) infection in an animal is provided. The method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein. The previously described embodiments of the method for inducing an immune response are applicable to the method of preventing an IAV infection described herein. [0081] In an illustrative aspect, an amino acid sequence comprising a consensus H3 hemagglutinin polypeptide is provided. [0082] In an embodiment, the consensus H3 hemagglutinin polypeptide comprises SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3. [0083] In an illustrative aspect, a nucleotide sequence comprising a nucleic acid sequence encoding a consensus H3 hemagglutinin polypeptide is provided. [0084] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the 85007-399822 -34- nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. [0085] In an embodiment, the consensus H3 hemagglutinin polypeptide comprises SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the consensus H3 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3. [0086] In an illustrative aspect, a recombinant polynucleotide is provided. The recombinant polynucleotide comprises a heterologous regulatory element operably linked to a nucleic acid sequence encoding a consensus H3 hemagglutinin polypeptide. 85007-399822 -35- [0087] The previously described embodiments of the consensus H3 hemagglutinin polypeptide are applicable to the recombinant polynucleotide described herein. The previously described embodiments of the nucleic acid sequence are applicable to the recombinant polynucleotide described herein. In an embodiment, the heterologous regulatory element is a promoter that functions in prokaryotic cells. [0088] In an illustrative aspect, a composition comprising a consensus H3 hemagglutinin polypeptide and a vector is provided. [0089] In an embodiment, the consensus H3 hemagglutinin polypeptide comprises an amino acid sequence. In an embodiment, the amino acid sequence comprises SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3. [0090] In an embodiment, the consensus H3 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H3 hemagglutinin polypeptide. [0091] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ 85007-399822 -36- ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4. In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. [0092] In an embodiment, the vector is a viral vector. In an embodiment, the viral vector is an ORFV vector. In an embodiment, the ORFV vector does not comprise ORFV121. [0093] In an embodiment, the vector is a nucleic acid vector. In an embodiment, the nucleic acid vector is a DNA vector. In an embodiment, the nucleic acid vector is a RNA vector. [0094] In an illustrative aspect, a pharmaceutical composition is provided. The pharmaceutical composition comprises i) a consensus H3 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers. [0095] In an embodiment, the consensus H3 hemagglutinin polypeptide is comprised in the composition according to a corresponding embodiment described herein. [0096] In an embodiment, the consensus H3 hemagglutinin polypeptide comprises an amino acid sequence. The previously described embodiments of the amino acid sequence are applicable to the pharmaceutical composition described herein. [0097] In an embodiment, the consensus H3 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H3 hemagglutinin polypeptide. The previously described embodiments of the nucleic acid sequence are applicable to the pharmaceutical composition described herein. 85007-399822 -37- [0098] The previously described embodiments related to pharmaceutical compositions are applicable to the additional pharmaceutical compositions described herein. [0099] In an illustrative aspect, a method for inducing an immune response in an animal against an influenza A virus (IAV) is provided. The method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein. [00100] The previously described embodiments of the methods for inducing an immune response are applicable to the additional methods for inducing an immune response described herein. [00101] In an illustrative aspect, a method of preventing an influenza A virus (IAV) infection in an animal is provided. The method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein. [00102] The previously described embodiments of the method for inducing an immune response are applicable to the method of preventing an IAV infection described herein. [00103] In an illustrative aspect, an amino acid sequence comprising a chimeric polypeptide is provided. A chimeric polypeptide can include molecules comprising a first portion of an IAV polypeptide and a second portion of an IAV polypeptide. The first portion and the second portion can be derived from different IAV subtypes, for instance H1, H3, H6, H8, H14, and H15. Any such portions can be prepared from the proteins by standard biochemical methods, or by expressing a polynucleotide encoding one or more portions/fragments. For instance, the first portion can comprise a stalk region of a contemporary H1 or H3 IAV strain and the second portion can comprise a head region (e.g., an exotic head region) derived from one of H6, H8, H14, and H15 subtypes. [00104] In an embodiment, the chimeric polypeptide comprise a contemporary region and a head region. In an embodiment, the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H6 85007-399822 -38- contemporary polypeptide. In an embodiment, the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H8 contemporary polypeptide. In an embodiment, the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H14 contemporary polypeptide. In an embodiment, the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H15 contemporary polypeptide. [00105] In an embodiment, the chimeric polypeptide comprises SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 5. In an embodiment, the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 5. [00106] In an embodiment, the chimeric polypeptide comprises SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 97% sequence identity to the 85007-399822 -39- sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 7. In an embodiment, the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 7. [00107] In an embodiment, the chimeric polypeptide comprises SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 9. In an embodiment, the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 9. [00108] In an embodiment, the chimeric polypeptide comprises SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 11. In an embodiment, 85007-399822 -40- the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 11. [00109] In an illustrative aspect, a nucleotide sequence comprising a nucleic acid sequence encoding a chimeric polypeptide is provided. In an embodiment, the chimeric polypeptide comprise a contemporary region and a head region. In an embodiment, the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H6 contemporary polypeptide. In an embodiment, the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H8 contemporary polypeptide. In an embodiment, the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H14 contemporary polypeptide. In an embodiment, the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H15 contemporary polypeptide. [00110] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 6. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 6. [00111] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises 85007-399822 -41- at least 85% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 8. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 8. [00112] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 10. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 10. [00113] In an embodiment, the nucleic acid sequence comprises SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 95% 85007-399822 -42- sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 12. In an embodiment, the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 12. [00114] In an embodiment, the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. [00115] The previously described embodiments of the chimeric polypeptide for the amino acid sequence are applicable to the nucleotide sequence as described herein. [00116] In an illustrative aspect, a recombinant polynucleotide is provided. The recombinant polynucleotide comprises a heterologous regulatory element operably linked to a nucleic acid sequence encoding a chimeric polypeptide. [00117] The previously described embodiments of the chimeric polypeptide for the amino acid sequence are applicable to the recombinant polynucleotide as described herein. [00118] In an illustrative aspect, a composition comprising a chimeric polypeptide and a vector is provided. The previously described embodiments of the chimeric polypeptide for the amino acid sequence are applicable to the composition as described herein. The previously described embodiments of the nucleic acid sequence are applicable to the composition as described herein. [00119] In an embodiment, the vector is a viral vector. In an embodiment, the viral vector is an ORFV vector. In an embodiment, the ORFV vector does not comprise ORFV121. [00120] In an embodiment, the vector is a nucleic acid vector. In an embodiment, the nucleic acid vector is a DNA vector. In an embodiment, the nucleic acid vector is a RNA vector. 85007-399822 -43- [00121] In an illustrative aspect, a pharmaceutical composition is provided. The pharmaceutical composition comprises i) a chimeric polypeptide and ii) one or more pharmaceutically acceptable carriers. [00122] In an embodiment, the chimeric polypeptide is comprised in the composition of according to a corresponding embodiment described herein. [00123] The previously described embodiments of the chimeric polypeptide for the amino acid sequence are applicable to the pharmaceutical composition as described herein. The previously described embodiments of the nucleic acid sequence are applicable to the pharmaceutical composition as described herein. [00124] The previously described embodiments related to pharmaceutical compositions are applicable to the additional pharmaceutical compositions described herein. [00125] In an illustrative aspect, a method for inducing an immune response in an animal against an influenza A virus (IAV) is provided. The method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein. [00126] The previously described embodiments of the methods for inducing an immune response are applicable to the additional methods for inducing an immune response described herein. [00127] In an illustrative aspect, a method of preventing an influenza A virus (IAV) infection in an animal is provided. The method comprises the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition according to a corresponding embodiment described herein. [00128] The previously described embodiments of the method for inducing an immune response are applicable to the method of preventing an IAV infection described herein. [00129] The following numbered embodiments are contemplated and are non- limiting: 1. An amino acid sequence comprising a consensus H1 hemagglutinin polypeptide. 85007-399822 -44- 2. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1. 3. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. 4. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. 5. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. 6. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. 7. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. 8. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. 9. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. 10. The amino acid sequence of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. 11. A nucleotide sequence comprising a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide. 85007-399822 -45- 12. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 2. 13. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2. 14. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2. 15. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2. 16. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2. 17. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. 18. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. 19. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. 20. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2. 21. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 85007-399822 -46- 22. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1. 23. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. 24. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. 25. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. 26. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. 27. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. 28. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. 29. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. 30. The nucleotide of clause 11, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. 85007-399822 -47- 31. A recombinant polynucleotide comprising a heterologous regulatory element operably linked to a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide. 32. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1. 33. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. 34. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. 35. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. 36. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. 37. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. 38. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. 39. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. 85007-399822 -48- 40. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. 41. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the heterologous regulatory element is a promoter that functions in prokaryotic cells. 42. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 2. 43. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2. 44. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2. 45. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2. 46. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2. 47. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. 48. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. 85007-399822 -49- 49. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. 50. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2. 51. The recombinant polynucleotide of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 52. A composition comprising a consensus H1 hemagglutinin polypeptide and a vector. 53. The composition of clause 52, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence. 54. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises SEQ ID NO: 1. 55. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. 56. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. 57. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. 58. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. 85007-399822 -50- 59. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. 60. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. 61. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. 62. The composition of clause 53, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. 63. The composition of clause 52, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H1 hemagglutinin polypeptide. 64. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 2. 65. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2. 66. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2. 67. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2. 68. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2. 85007-399822 -51- 69. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. 70. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. 71. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. 72. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2. 73. The composition of clause 63, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 74. The composition of clause 52, any other suitable clause, or any combination of suitable clauses, wherein the vector is a viral vector. 75. The composition of clause 74, any other suitable clause, or any combination of suitable clauses, wherein the viral vector is an ORFV vector. 76. The composition of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the ORFV vector does not comprise ORFV121. 77. The composition of clause 52, any other suitable clause, or any combination of suitable clauses, wherein the vector is a nucleic acid vector. 78. The composition of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid vector is a DNA vector. 79. The composition of clause 77, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid vector is a RNA vector. 80. A pharmaceutical composition comprising i) a consensus H1 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers. 85007-399822 -52- 81. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide is comprised in the composition of any one of clauses 52 to 79. 82. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence. 83. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises SEQ ID NO: 1. 84. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 1. 85. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 1. 86. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. 87. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. 88. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 1. 89. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 1. 85007-399822 -53- 90. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 1. 91. The pharmaceutical composition of clause 82, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 1. 92. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the consensus H1 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H1 hemagglutinin polypeptide. 93. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 2. 94. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 2. 95. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 2. 96. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2. 97. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2. 98. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 2. 85007-399822 -54- 99. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 2. 100. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 2. 101. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 2. 102. The pharmaceutical composition of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 103. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is an oral formulation. 104. The pharmaceutical composition of clause 103, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 105. The pharmaceutical composition of clause 103, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 106. The pharmaceutical composition of clause 103, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 107. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is a parenteral formulation. 108. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is selected from the 85007-399822 -55- group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 109. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 110. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 111. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 112. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 113. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 114. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 115. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 116. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 117. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 118. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 119. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 120. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 85007-399822 -56- 121. The pharmaceutical composition of clause 107, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 122. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition further comprises a second therapeutic agent. 123. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a vaccine. 124. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a single dose. 125. The pharmaceutical composition of clause 80, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a single unit dose. 126. A method for inducing an immune response in an animal against an influenza A virus (IAV), the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 80 to 125. 127. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a Cytotoxic T lymphocyte (CTL) response. 128. The method of clause 127, any other suitable clause, or any combination of suitable clauses, wherein the CTL response is an IAV-specific response. 129. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises an IgG response. 130. The method of clause 129, any other suitable clause, or any combination of suitable clauses, wherein the IgG response is an IAV-specific response. 131. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a T cell response. 85007-399822 -57- 132. The method of clause 131, any other suitable clause, or any combination of suitable clauses, wherein the T cell response is an IAV-specific response. 133. The method of clause 131, any other suitable clause, or any combination of suitable clauses, wherein the T cell response comprises CD8+ T cells. 134. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a T-helper/memory cell response. 135. The method of clause 134, any other suitable clause, or any combination of suitable clauses, wherein the T-helper/memory cell response is an IAV-specific response. 136. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises an IFN-γ response. 137. The method of clause 136, any other suitable clause, or any combination of suitable clauses, wherein the IFN-γ response is an IAV-specific response. 138. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the administration is a prophylactic administration to the animal. 139. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the animal is a mammal. 140. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the animal is a porcine. 141. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1 subtype. 142. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3 subtype. 143. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N1 subtype. 144. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N2 subtype. 85007-399822 -58- 145. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3N2 subtype. 146. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV viral load of the animal. 147. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV virus shedding by the animal. 148. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the administration is an oral administration. 149. The method of clause 148, any other suitable clause, or any combination of suitable clauses, wherein the oral administration is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 150. The method of clause 148, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 151. The method of clause 148, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 152. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the administration is a parenteral administration. 153. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 154. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 155. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 85007-399822 -59- 156. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 157. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 158. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 159. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 160. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 161. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 162. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 163. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 164. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 165. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 166. The method of clause 152, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 167. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single dose. 168. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single unit dose. 85007-399822 -60- 169. The method of clause 126, any other suitable clause, or any combination of suitable clauses, wherein the method further comprises administration of a second therapeutic agent to the animal. 170. A method of preventing an influenza A virus (IAV) infection in an animal, the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 80 to 125. 171. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the administration is a prophylactic administration to the animal. 172. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the animal is a mammal. 173. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the animal is a porcine. 174. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1 subtype. 175. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3 subtype. 176. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N1 subtype. 177. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N2 subtype. 178. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3N2 subtype. 179. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV viral load of the animal. 180. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV virus shedding by the animal. 85007-399822 -61- 181. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the administration is an oral administration. 182. The method of clause 181, any other suitable clause, or any combination of suitable clauses, wherein the oral administration is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 183. The method of clause 181, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 184. The method of clause 181, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 185. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the administration is a parenteral administration. 186. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 187. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 188. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 189. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 190. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 191. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 192. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 85007-399822 -62- 193. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 194. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 195. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 196. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 197. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 198. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 199. The method of clause 185, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 200. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single dose. 201. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single unit dose. 202. The method of clause 170, any other suitable clause, or any combination of suitable clauses, wherein the method further comprises administration of a second therapeutic agent to the animal. 203. An amino acid sequence comprising a consensus H3 hemagglutinin polypeptide. 204. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises SEQ ID NO: 3. 85007-399822 -63- 205. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3. 206. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. 207. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. 208. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. 209. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. 210. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. 211. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. 212. The amino acid sequence of clause 203, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3. 213. A nucleotide sequence comprising a nucleic acid sequence encoding a consensus H3 hemagglutinin polypeptide. 214. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 4. 85007-399822 -64- 215. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4. 216. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. 217. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. 218. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 219. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. 220. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. 221. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. 222. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4. 223. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 85007-399822 -65- 224. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises SEQ ID NO: 3. 225. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3. 226. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. 227. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. 228. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. 229. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. 230. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. 231. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. 232. The nucleotide sequence of clause 213, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3. 85007-399822 -66- 233. A recombinant polynucleotide comprising a heterologous regulatory element operably linked to a nucleic acid sequence encoding a consensus H3 hemagglutinin polypeptide. 234. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises SEQ ID NO: 3. 235. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3. 236. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. 237. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. 238. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. 239. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. 240. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. 241. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. 85007-399822 -67- 242. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3. 243. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the heterologous regulatory element is a promoter that functions in prokaryotic cells. 244. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 4. 245. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4. 246. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. 247. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. 248. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 249. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. 250. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. 85007-399822 -68- 251. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. 252. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4. 253. The recombinant polynucleotide of clause 233, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 254. A composition comprising a consensus H3 hemagglutinin polypeptide and a vector. 255. The composition of clause 254, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises an amino acid sequence. 256. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises SEQ ID NO: 3. 257. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3. 258. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. 259. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. 260. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. 85007-399822 -69- 261. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. 262. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. 263. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. 264. The composition of clause 255, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3. 265. The composition of clause 254, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H3 hemagglutinin polypeptide. 266. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 4. 267. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4. 268. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. 269. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. 270. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 85007-399822 -70- 271. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. 272. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. 273. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. 274. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4. 275. The composition of clause 265, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 276. The composition of clause 254, any other suitable clause, or any combination of suitable clauses, wherein the vector is a viral vector. 277. The composition of clause 276, any other suitable clause, or any combination of suitable clauses, wherein the viral vector is an ORFV vector. 278. The composition of clause 277, any other suitable clause, or any combination of suitable clauses, wherein the ORFV vector does not comprise ORFV121. 279. The composition of clause 254, any other suitable clause, or any combination of suitable clauses, wherein the vector is a nucleic acid vector. 280. The composition of clause 279, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid vector is a DNA vector. 281. The composition of clause 279, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid vector is a RNA vector. 282. A pharmaceutical composition comprising i) a consensus H3 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers. 85007-399822 -71- 283. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide is comprised in the composition of any one of clauses 254 to 281. 284. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises an amino acid sequence. 285. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises SEQ ID NO: 3. 286. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 3. 287. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 3. 288. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. 289. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. 290. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 3. 291. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 3. 85007-399822 -72- 292. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 3. 293. The pharmaceutical composition of clause 284, any other suitable clause, or any combination of suitable clauses, wherein the amino acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 3. 294. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the consensus H3 hemagglutinin polypeptide comprises a nucleic acid sequence encoding the consensus H3 hemagglutinin polypeptide. 295. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 4. 296. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 4. 297. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 4. 298. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. 299. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 300. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 4. 85007-399822 -73- 301. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 4. 302. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 4. 303. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 4. 304. The pharmaceutical composition of clause 294, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 305. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is an oral formulation. 306. The pharmaceutical composition of clause 305, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 307. The pharmaceutical composition of clause 305, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 308. The pharmaceutical composition of clause 305, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 309. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is a parenteral formulation. 310. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is selected from the 85007-399822 -74- group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 311. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 312. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 313. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 314. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 315. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 316. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 317. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 318. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 319. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 320. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 321. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 322. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 85007-399822 -75- 323. The pharmaceutical composition of clause 309, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 324. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition further comprises a second therapeutic agent. 325. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a vaccine. 326. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a single dose. 327. The pharmaceutical composition of clause 282, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a single unit dose. 328. A method for inducing an immune response in an animal against an influenza A virus (IAV), the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 282 to 327. 329. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a Cytotoxic T lymphocyte (CTL) response. 330. The method of clause 329, any other suitable clause, or any combination of suitable clauses, wherein the CTL response is an IAV-specific response. 331. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises an IgG response. 332. The method of clause 331, any other suitable clause, or any combination of suitable clauses, wherein the IgG response is an IAV-specific response. 333. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a T cell response. 85007-399822 -76- 334. The method of clause 333, any other suitable clause, or any combination of suitable clauses, wherein the T cell response is an IAV-specific response. 335. The method of clause 333, any other suitable clause, or any combination of suitable clauses, wherein the T cell response comprises CD8+ T cells. 336. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a T-helper/memory cell response. 337. The method of clause 336, any other suitable clause, or any combination of suitable clauses, wherein the T-helper/memory cell response is an IAV-specific response. 338. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises an IFN-γ response. 339. The method of clause 338, any other suitable clause, or any combination of suitable clauses, wherein the IFN-γ response is an IAV-specific response. 340. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the administration is a prophylactic administration to the animal. 341. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the animal is a mammal. 342. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the animal is a porcine. 343. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1 subtype. 344. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3 subtype. 345. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N1 subtype. 346. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N2 subtype. 85007-399822 -77- 347. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3N2 subtype. 348. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV viral load of the animal. 349. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV virus shedding by the animal. 350. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the administration is an oral administration. 351. The method of clause 350, any other suitable clause, or any combination of suitable clauses, wherein the oral administration is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 352. The method of clause 350, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 353. The method of clause 350, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 354. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the administration is a parenteral administration. 355. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 356. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 357. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 85007-399822 -78- 358. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 359. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 360. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 361. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 362. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 363. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 364. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 365. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 366. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 367. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 368. The method of clause 354, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 369. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single dose. 370. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single unit dose. 85007-399822 -79- 371. The method of clause 328, any other suitable clause, or any combination of suitable clauses, wherein the method further comprises administration of a second therapeutic agent to the animal. 372. A method of preventing an influenza A virus (IAV) infection in an animal, the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 282 to 327. 373. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the administration is a prophylactic administration to the animal. 374. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the animal is a mammal. 375. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the animal is a porcine. 376. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1 subtype. 377. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3 subtype. 378. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N1 subtype. 379. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N2 subtype. 380. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3N2 subtype. 381. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV viral load of the animal. 382. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV virus shedding by the animal. 85007-399822 -80- 383. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the administration is an oral administration. 384. The method of clause 383, any other suitable clause, or any combination of suitable clauses, wherein the oral administration is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 385. The method of clause 383, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 386. The method of clause 383, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 387. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the administration is a parenteral administration. 388. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 389. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 390. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 391. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 392. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 393. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 394. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 85007-399822 -81- 395. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 396. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 397. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 398. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 399. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 400. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 401. The method of clause 387, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 402. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single dose. 403. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single unit dose. 404. The method of clause 372, any other suitable clause, or any combination of suitable clauses, wherein the method further comprises administration of a second therapeutic agent to the animal. 405. An amino acid sequence comprising a chimeric polypeptide. 406. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprise a contemporary region and a head region. 407. The amino acid sequence of clause 406, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H1 85007-399822 -82- hemagglutinin contemporary polypeptide and the head region comprises a H6 contemporary polypeptide. 408. The amino acid sequence of clause 406, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H8 contemporary polypeptide. 409. The amino acid sequence of clause 406, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H14 contemporary polypeptide. 410. The amino acid sequence of clause 406, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H15 contemporary polypeptide. 411. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 5. 412. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. 413. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 5. 414. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 5. 415. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 5. 85007-399822 -83- 416. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 5. 417. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 5. 418. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 5. 419. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 5. 420. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 7. 421. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 7. 422. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. 423. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 7. 424. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 7. 85007-399822 -84- 425. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 7. 426. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 7. 427. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 7. 428. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 7. 429. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 9. 430. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 9. 431. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 9. 432. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 9. 433. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 9. 85007-399822 -85- 434. The method of clause 405, any other suitable clause, or any combination of suitable clauses acid sequence, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 9. 435. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 9. 436. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 9. 437. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 9. 438. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 11. 439. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 11. 440. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 11. 441. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 11. 442. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 11. 85007-399822 -86- 443. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 11. 444. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 11. 445. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 11. 446. The amino acid sequence of clause 405, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 11. 447. A nucleotide sequence comprising a nucleic acid sequence encoding a chimeric polypeptide. 448. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprise a contemporary region and a head region. 449. The nucleotide sequence of clause 448, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H6 contemporary polypeptide. 450. The nucleotide sequence of clause 448, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H8 contemporary polypeptide. 451. The nucleotide sequence of clause 448, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H14 contemporary polypeptide. 85007-399822 -87- 452. The nucleotide sequence of clause 448, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H15 contemporary polypeptide. 453. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 6. 454. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 6. 455. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 6. 456. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 6. 457. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 6. 458. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 6. 459. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 6. 460. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 6. 85007-399822 -88- 461. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 6. 462. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 8. 463. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 8. 464. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 8. 465. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 8. 466. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 8. 467. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 8. 468. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 8. 469. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 8. 85007-399822 -89- 470. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 8. 471. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 10. 472. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 10. 473. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 10. 474. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 10. 475. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 10. 476. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 10. 477. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 10. 478. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 10. 85007-399822 -90- 479. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 10. 480. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 12. 481. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 12. 482. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 12. 483. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 12. 484. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 12. 485. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 12. 486. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 12. 487. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 12. 85007-399822 -91- 488. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 12. 489. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 490. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 5. 491. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. 492. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 5. 493. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 5. 494. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 5. 495. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 5. 496. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 5. 85007-399822 -92- 497. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 5. 498. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 5. 499. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 7. 500. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 7. 501. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. 502. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 7. 503. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 7. 504. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 7. 505. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 7. 85007-399822 -93- 506. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 7. 507. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 7. 508. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 9. 509. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 9. 510. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 9. 511. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 9. 512. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 9. 513. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 9. 514. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 9. 85007-399822 -94- 515. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 9. 516. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 9. 517. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 11. 518. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 11. 519. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 11. 520. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 11. 521. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 11. 522. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 11. 523. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 11. 85007-399822 -95- 524. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 11. 525. The nucleotide sequence of clause 447, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 11. 526. A recombinant polynucleotide comprising a heterologous regulatory element operably linked to a nucleic acid sequence encoding a chimeric polypeptide. 527. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprise a contemporary region and a head region. 528. The recombinant polynucleotide of clause 527, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H6 contemporary polypeptide. 529. The recombinant polynucleotide of clause 527, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H1 hemagglutinin contemporary polypeptide and the head region comprises a H8 contemporary polypeptide. 530. The recombinant polynucleotide of clause 527, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H14 contemporary polypeptide. 531. The recombinant polynucleotide of clause 527, any other suitable clause, or any combination of suitable clauses, wherein the contemporary region comprises a H3 hemagglutinin contemporary polypeptide and the head region comprises a H15 contemporary polypeptide. 85007-399822 -96- 532. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 5. 533. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. 534. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 5. 535. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 5. 536. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 5. 537. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 5. 538. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 5. 539. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 5. 540. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 5. 85007-399822 -97- 541. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 7. 542. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 7. 543. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. 544. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 7. 545. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 7. 546. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 7. 547. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 7. 548. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 7. 549. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 7. 85007-399822 -98- 550. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 9. 551. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 9. 552. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 9. 553. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 9. 554. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 9. 555. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 9. 556. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 9. 557. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 9. 558. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 9. 85007-399822 -99- 559. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 11. 560. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 11. 561. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 11. 562. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 11. 563. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 11. 564. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 11. 565. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 11. 566. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 11. 567. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 11. 85007-399822 -100- 568. The recombinant polynucleotide of clause 526, any other suitable clause, or any combination of suitable clauses, wherein the heterologous regulatory element is a promoter that functions in prokaryotic cells. 569. A composition comprising a chimeric polypeptide and a vector. 570. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 5. 571. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. 572. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 5. 573. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 5. 574. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 5. 575. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 5. 576. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 5. 577. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 5. 85007-399822 -101- 578. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 5. 579. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 7. 580. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 7. 581. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. 582. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 7. 583. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 7. 584. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 7. 585. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 7. 586. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 7. 587. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 7. 85007-399822 -102- 588. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 9. 589. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 9. 590. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 9. 591. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 9. 592. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 9. 593. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 9. 594. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 9. 595. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 9. 596. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 9. 597. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 11. 85007-399822 -103- 598. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 11. 599. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 11. 600. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 11. 601. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 11. 602. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 11. 603. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 11. 604. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 11. 605. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 11. 606. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises a nucleic acid sequence encoding the chimeric polypeptide. 607. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 6. 85007-399822 -104- 608. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 6. 609. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 6. 610. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 6. 611. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 6. 612. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 6. 613. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 6. 614. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 6. 615. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 6. 616. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 8. 617. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 8. 85007-399822 -105- 618. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 8. 619. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 8. 620. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 8. 621. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 8. 622. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 8. 623. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 8. 624. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 8. 625. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 10. 626. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 10. 627. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 10. 85007-399822 -106- 628. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 10. 629. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 10. 630. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 10. 631. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 10. 632. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 10. 633. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 10. 634. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 12. 635. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 12. 636. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 12. 637. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 12. 85007-399822 -107- 638. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 12. 639. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 12. 640. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 12. 641. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 12. 642. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 12. 643. The composition of clause 606, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 644. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the vector is a viral vector. 645. The composition of clause 644, any other suitable clause, or any combination of suitable clauses, wherein the viral vector is an ORFV vector. 646. The composition of clause 645, any other suitable clause, or any combination of suitable clauses, wherein the ORFV vector does not comprise ORFV121. 647. The composition of clause 569, any other suitable clause, or any combination of suitable clauses, wherein the vector is a nucleic acid vector. 648. The composition of clause 647, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid vector is a DNA vector. 85007-399822 -108- 649. The composition of clause 647, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid vector is a RNA vector. 650. A pharmaceutical composition comprising i) a chimeric polypeptide and ii) one or more pharmaceutically acceptable carriers. 651. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide is comprised in the composition of any one of clauses 569 to 649. 652. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 5. 653. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 5. 654. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 5. 655. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 5. 656. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 5. 657. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 5. 658. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 5. 85007-399822 -109- 659. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 5. 660. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 5. 661. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 7. 662. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 7. 663. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 7. 664. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 7. 665. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 7. 666. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 7. 667. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 7. 85007-399822 -110- 668. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 7. 669. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 7. 670. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 9. 671. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 9. 672. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 9. 673. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 9. 674. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 9. 675. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 9. 676. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 9. 85007-399822 -111- 677. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 9. 678. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 9. 679. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises SEQ ID NO: 11. 680. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 80% sequence identity to the sequence of SEQ ID NO: 11. 681. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 85% sequence identity to the sequence of SEQ ID NO: 11. 682. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 11. 683. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 11. 684. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 96% sequence identity to the sequence of SEQ ID NO: 11. 685. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 97% sequence identity to the sequence of SEQ ID NO: 11. 85007-399822 -112- 686. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 98% sequence identity to the sequence of SEQ ID NO: 11. 687. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises at least 99% sequence identity to the sequence of SEQ ID NO: 11. 688. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the chimeric polypeptide comprises a nucleic acid sequence encoding the chimeric polypeptide. 689. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 6. 690. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 6. 691. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 6. 692. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 6. 693. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 6. 694. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 6. 85007-399822 -113- 695. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 6. 696. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 6. 697. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 6. 698. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 8. 699. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 8. 700. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 8. 701. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 8. 702. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 8. 703. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 8. 85007-399822 -114- 704. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 8. 705. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 8. 706. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 8. 707. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 10. 708. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 10. 709. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 10. 710. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 10. 711. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 10. 712. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 10. 85007-399822 -115- 713. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 10. 714. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 10. 715. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 10. 716. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises SEQ ID NO: 12. 717. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 80% sequence identity to the sequence of SEQ ID NO: 12. 718. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 85% sequence identity to the sequence of SEQ ID NO: 12. 719. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 12. 720. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 12. 721. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 96% sequence identity to the sequence of SEQ ID NO: 12. 85007-399822 -116- 722. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 97% sequence identity to the sequence of SEQ ID NO: 12. 723. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 98% sequence identity to the sequence of SEQ ID NO: 12. 724. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence comprises at least 99% sequence identity to the sequence of SEQ ID NO: 12. 725. The pharmaceutical composition of clause 688, any other suitable clause, or any combination of suitable clauses, wherein the nucleic acid sequence is a native sequence that has been modified to comprise codons optimized for expression in prokaryotic cells. 726. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is an oral formulation. 727. The pharmaceutical composition of clause 726, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 728. The pharmaceutical composition of clause 726, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 729. The pharmaceutical composition of clause 726, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 730. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is a parenteral formulation. 731. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is selected from the 85007-399822 -117- group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 732. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 733. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 734. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 735. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 736. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 737. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 738. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 739. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 740. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 741. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 742. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 743. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 85007-399822 -118- 744. The pharmaceutical composition of clause 730, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 745. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition further comprises a second therapeutic agent. 746. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a vaccine. 747. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a single dose. 748. The pharmaceutical composition of clause 650, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is formulated as a single unit dose. 749. A method for inducing an immune response in an animal against an influenza A virus (IAV), the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 650 to 748. 750. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a Cytotoxic T lymphocyte (CTL) response. 751. The method of clause 750, any other suitable clause, or any combination of suitable clauses, wherein the CTL response is an IAV-specific response. 752. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises an IgG response. 753. The method of clause 752, any other suitable clause, or any combination of suitable clauses, wherein the IgG response is an IAV-specific response. 754. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a T cell response. 85007-399822 -119- 755. The method of clause 754, any other suitable clause, or any combination of suitable clauses, wherein the T cell response is an IAV-specific response. 756. The method of clause 754, any other suitable clause, or any combination of suitable clauses, wherein the T cell response comprises CD8+ T cells. 757. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises a T-helper/memory cell response. 758. The method of clause 757, any other suitable clause, or any combination of suitable clauses, wherein the T-helper/memory cell response is an IAV-specific response. 759. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises an IFN-γ response. 760. The method of clause 759, any other suitable clause, or any combination of suitable clauses, wherein the IFN-γ response is an IAV-specific response. 761. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the administration is a prophylactic administration to the animal. 762. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the animal is a mammal. 763. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the animal is a porcine. 764. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1 subtype. 765. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3 subtype. 766. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N1 subtype. 767. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N2 subtype. 85007-399822 -120- 768. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3N2 subtype. 769. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV viral load of the animal. 770. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV virus shedding by the animal. 771. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the administration is an oral administration. 772. The method of clause 771, any other suitable clause, or any combination of suitable clauses, wherein the oral administration is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 773. The method of clause 771, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 774. The method of clause 771, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 775. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the administration is a parenteral administration. 776. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 777. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 778. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 85007-399822 -121- 779. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 780. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 781. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 782. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 783. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 784. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 785. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 786. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 787. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 788. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 789. The method of clause 775, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 790. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single dose. 791. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single unit dose. 85007-399822 -122- 792. The method of clause 749, any other suitable clause, or any combination of suitable clauses, wherein the method further comprises administration of a second therapeutic agent to the animal. 793. A method of preventing an influenza A virus (IAV) infection in an animal, the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of clauses 650 to 748. 794. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the administration is a prophylactic administration to the animal. 795. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the animal is a mammal. 796. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the animal is a porcine. 797. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1 subtype. 798. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3 subtype. 799. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N1 subtype. 800. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H1N2 subtype. 801. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the IAV is an IAV H3N2 subtype. 802. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV viral load of the animal. 803. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the method comprises a reduction in IAV virus shedding by the animal. 85007-399822 -123- 804. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the administration is an oral administration. 805. The method of clause 804, any other suitable clause, or any combination of suitable clauses, wherein the oral administration is selected from the group consisting of a tablet, a capsule, a suspension, an emulsion, a syrup, a colloidal dispersion, a dispersion, and an effervescent composition. 806. The method of clause 804, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a suspension. 807. The method of clause 804, any other suitable clause, or any combination of suitable clauses, wherein the oral formulation is a reconstitutable suspension. 808. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the administration is a parenteral administration. 809. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral administration is selected from the group consisting of intravenous, intraarterial, intraperitoneal, intrathecal, intradermal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intratumoral, intramuscular and subcutaneous. 810. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intravenous. 811. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraarterial. 812. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraperitoneal. 813. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrathecal. 814. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intradermal. 815. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is epidural. 85007-399822 -124- 816. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracerebroventricular. 817. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intraurethral. 818. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intrasternal. 819. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intracranial. 820. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intratumoral. 821. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is intramuscular. 822. The method of clause 808, any other suitable clause, or any combination of suitable clauses, wherein the parenteral formulation is subcutaneous. 823. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single dose. 824. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the pharmaceutical composition is administered as a single unit dose. 825. The method of clause 793, any other suitable clause, or any combination of suitable clauses, wherein the method further comprises administration of a second therapeutic agent to the animal. EXAMPLES EXAMPLE 1 Experimental Methods and Materials 85007-399822 -125- Cells and viruses [00130] Primary ovine fetal turbinate (OFTu), swine turbinate cells (STU) and Madin-Darby Canine Kidney (MDCK) cells) cells were cultured at 37 °C with 5% CO2 in minimum essential medium (MEM) or Dulbeco’s Modified Eagle medium (DMEM) supplemented with 10% FBS, 2 mM L-glutamine and containing penicillin (100 U ml -1), streptomycin (100 µg ml -1) and gentamicin (50 µg ml -1). ORFV strain IA82 (OV-IA82) (provided by Dr. Daniel Rock at University of Illinois at Urbana-Champaign), was used as the parental virus to construct the recombinant ORFV expressing the Influenza A virus of Swine (IAV-S) consensus H1 glycoprotein (HA). Swine influenza virus H1N1 A/Swine/OH/24366/2007 (provided by Dr. Gourapura lab at OSU), a H1N1 virus, belonging to clade gamma, and pandemic H1N1 A/California/04/2009 (obtained from National Veterinary Services Laboratory [NVSL], Ames, Iowa), belonging to the clade “new pandemic” (npdm), were used for virus challenge, and antigen for whole virus ELISA. Both H1N1 viruses were propagated in MDCK cells using DMEM containing TPCK-treated trypsin (2 µg ml -1) and 25 mM HEPES buffer. All the IAV-S isolates used in cross-reactivity assays were obtained from NVSL. These isolates included: A/Swine/Iowa/A02424852/2020 (Clade gamma), A/Swine/South Dakota/A02156993/2018 (Clade gamma-2-beta-like), A/Swine/Missouri/A02479312/2020 (Clade npdm), A/Swine/Michigan/A02524810/2020 (Clade npdm), A/Swine/Texas/A02245632/2020 (Clade beta), A/Swine/Oklahoma/A02245707/2020 (Clade beta), A/Swine/Minnesota/A01785306/2017 (Clade alpha), A/Swine/Iowa/A02479151/2020 (Clade delta 1), A/Swine/Oklahoma/A02214419/2017 (Clade delta 1), and A/Swine/South Dakota/A02524887/2020 (Clade gamma). More information regarding these isolates are presented in Table 2. Table 2. Information regarding the IAV-S isolates used for the ELISAs, including the percent nucleotide (nt) and amino acid (aa) pairwise identities to the conH1 sequence. Info Missouri/20 Oklahoma/17 Oklahoma/20 85007-399822 -126- clade npdm delta 1 beta year 2020 2017 2020 ab e (cont nued) Info South Dakota/18 South Dakota/20 Texas/20 Table 2 (continued) Info Ohio/07 California/09 Iowa/20 85007-399822 -127- Aa pairwise id 89.8 85.9 88.3 conH1 (%) Construction of recombinant plasmids [00131] The consensus full-length coding sequence of HA from H1 subtype (conH1) was generated in silico after analysis and alignment of a final set of 63 sequences of IAV-S isolated between 2014-2017 from H1 subtype obtained from clinical diagnostic cases at the South Dakota Animal Disease Research and Diagnostic Laboratory (Table 3). Restriction endonuclease sites required for insertion into the ORFV121 locus of the ORFV genome and early poxviral transcription termination signals (TTTTTNT) were removed from the conH1 sequence through silent nucleotide substitutions. The flag-tag epitope coding sequence was added to the 5’ of the HA consensus coding sequence under the control of the vaccinia virus late I1L promoter. Finally, the coding sequences of the restriction sites for HindIII and SalI were added to the 5’ and 3’ ends of the conH1. The DNA fragment containing the full-length of conH1 coding sequence under the control of the I1L promoter and Flag tag-epitope was chemically synthesized (GenScript®, Piscataway, NJ) and subcloned into the poxviral 85007-399822 -128- pUC57-ORFVΔ121-loxP-EGFP transfer vector, previously described. Correct cloning of conH1 was confirmed by restriction enzyme analysis in 1% agarose gel. Table 3. Set of the 63 HA sequences used for the nucleotide alignment that resulted in the conH1 sequence listed above. Access number Name Submission date KJ683871 A/ in /S th D k t /A01480750/2014 3/27/14 85007-399822 -129- KU942633 A/swine/Indiana/A01732606/2016 2/29/16 KU877392 A/swine/North Carolina/A01731797/2016 2/17/16 85007-399822 -130- MF455485 A/swine/Iowa/A02216640/2017 6/6/17 MF092761 A/swine/North Carolina/A02214480/2017 4/7/17 Generation and characterization of the recombinant viruses [00132] The full-length conH1 sequences was inserted into the ORFV121 locus of the ORFV genome by homologous recombination between the parental ORFV strain IA82 and the recombination cassette pUC57-ORFVΔ121-loxP-EGFP as previously described). The presence of conH1 and absence of ORFV121 sequence in purified recombinant virus were confirmed by PCR screening. Two pairs of internal primers were used for the PCR amplification of conH1, IAV-S-conH1-Fw-5’- ACTGCAAGCTTTATTTAAAAGTTGTTTGGTGAACTTAAATGGACTACAAAGAC GATGAGACAAGAAAG-3’ (SEQ ID. NO: 13) and IAV-S-conH1-Rv-5’- GAGGTGTCGACTTAAATACATATTCTACACTGTAAAGAC-3’ (SEQ ID. NO: 14) (1774 bp), and for the amplification of ORFV121 (401 bp), ORF121-int-Fw-5’- CCTCGGAAAAGAGCAGACAC-3’ (SEQ ID. NO: 15) and ORF121-int-Rv-5’- CTTCATCAGGCAGTCGTTCA-3’ (SEQ ID. NO: 16), followed by PCR amplicon analysis by electrophoresis in 1% agarose gel. Insertion and integrity of full-length conH1 and identity and integrity of ORFVΔ121 were further confirmed by sequencing on the Illumina Mi-Seq sequencing platform (Illumina, San Diego, CA) using Nextera XT DNA library preparation kit (Illumina, San Diego, CA). 85007-399822 -131- Expression of conH1 by the ORFVΔ121conH1 recombinant virus in vitro [00133] Expression of conH1 by the recombinant virus was assessed by indirect immunofluorescence assay (IFA), flow cytometry (FC) and Western blot (WB), as previously described. Briefly, for the IFA and FC, the expression of the heterologous protein in vitro, was assessed in permeabilized and non-permeabilized OFTu cells infected with the ORFVΔ121conH1 recombinant virus by using an anti-Flag-tag epitope monoclonal mouse antibody (GenScript®, Piscataway, NJ). [00134] For the IFA, Goat Anti-Mouse IgG Monoclonal Antibody DyLight® 594 (Bethyl Laboratories Inc., Montgomery, TX) at 1:300 was used as the secondary conjugated-antibody. All antibody dilutions were prepared in PBS with 1% bovine serum albumin (BSA), and the cells were visualized under a fluorescence microscope. [00135] For the FC, the antibodies were diluted in Perm/Wash 1x solution for use in permeabilized cells, or in FACS buffer for non-permeabilized cells. The negative control well just received FACS buffer without any antibody. After the 30 min of primary antibody incubation, cells were washed and probed with Alexa fluor 594 goat anti-mouse antibody (Invi-trogen, catalog no: A11005) at 1:300. Following the 30 min incubation, the cells were washed, resuspended with 150 µl of PBS 1x, and stored in the dark at 4ºC until data acquisition with an Attune NxT Flow Cytometer. Gates were adjusted based on the mock-infected cells. Gating and data analyses were performed using the FlowJo software (Version 10.8.2, Tree Star Inc., Ashland, OR, USA). [00136] Expression of conH1 by the ORFVΔ121conH1 recombinant virus was also assessed by Western blot. Briefly, OFTu cells cultured in 6-well plates and were infected with a high MOI of ORFVΔ121conH1 recombinant virus (MOI= 10) and harvested at 12, 24, 48 and 72 hpi. Non-infected OFTu cells were used as negative control. Cells were lysed and western blot performed as previously described. The constitutively expressed protein β-actin was chosen as loading controls for quantitative Western blotting. So, the membrane was incubated with a monoclonal antibody against β-actin (Santa Cruz Biotechnology Inc., Santa Cruz, CA) at 1:1000 for 2 h at 37°C. After washing, the 85007-399822 -132- membrane was incubated once again with IRDye 800CW-labeled secondary antibody for 1 h at 37° C, washed, and developed by ChemiDoc MP Imaging System (Bio-Rad, Hercules, CA). Stability of the ORFVΔ121conH1 recombinant virus in cell culture [00137] The stability of conH1 gene inserted into the ORFV121 locus of the ORFVΔ121conH1 genome was evaluated after serial passages (up to 10 passages) of the recombinant virus at 1 MOI in OFTu cells. After 10 passages, 24 well-plate containing OFTu cells were infected with approximately 1 MOI of the ORFVΔ121conH1 recombinant virus at passages 1, 5 or 10 and incubated for 24 hpi. Cells were then fixed and permeabilized and stained as described above except by the use of Goat Anti-Mouse IgG Monoclonal Antibody DyLight® 488 conjugate as the secondary antibody. Cross-reactivity of ORFVΔ121conH1 against divergent porcine H1N1 antisera [00138] The cross-reactivity between ORFVΔ121conH1 recombinant virus and serum of pigs infected with 3 different strains of H1N1 IAV-S was assessed in vitro. OFTu cells were plated in a 24 well-plate and infected with ORFVΔ121conH1 recombinant virus at 0.1 MOI for 48 hpi. After incubation, the cells were fixed, permeabilized with 0.2% Triton X-100-PBS and incubated with serial dilutions of the H1N1 antisera developed against A/Sw/CA/04/2009 (clade npdm), A/Sw/IL/00685/2005 (clade delta 2), or A/Sw/KY/02086/2008 (clade beta) strains. These anti-sera presented hemagglutination inhibition (HI) titers of 1:80, 1:160, and 1:80 against the homologous viruses, respectively. After 1 h incubation, the plate was washed with PBS (3 times) and incubated with an anti-swine IgG secondary antibody (DyLight® 488 conjugate) to be further visualized under a fluorescence microscope. Replication kinetics [00139] Replication properties of ORFVΔ121conH1 recombinant virus were assessed in vitro in OFTu and primary swine turbinate (STu) cells cultured in 12-well 85007-399822 -133- plates. Multistep (MOI = 0.1) and single step (MOI = 10) growth curves with ORFVΔ121conH1 were performed in OFTu cells. Cells were collected at 6, 12, 24, 48 and 72 hpi. Uninfected OFTu and STu were used as controls (0 hpi). Virus titers were determined on each time point using the Spearman and Karber’s method and expressed as tissue culture infectious dose 50 (TCID50) per milliliter. Assessment of protection against divergent H1N1 swine influenza viruses after [00140] The immunogenicity and protective efficacy of the recombinant virus against divergent strains were assessed in pigs. The viruses used for the challenge were A/Sw/OH/24366/2007 (H1N1) (OH07) and A/California/04/2009 (H1N1) (CA09) strain. Forty-one 3-week-old specific pathogen free pigs, seronegative for IAV, were randomly allocated to five experimental groups as follows: Group 1, sham- immunized/mock-challenged (n=6); Group 2, ORFVΔ121conH1 immunized/OH07 challenged (n=9); Group 3, ORFVΔ121conH1 immunized/CA09 challenged (n=9), Group 4, sham-immunized/CA09 challenged (n=9), and Group 5 sham-immunized/OH07 challenged (n=8) (Table 4). Table 4. Experimental design of animal immunization study Group n Immunization Immunogen titer Route Immunization days 1 6 Sham – Intramuscular 0, 21 DPV* 2 9 ORFVΔ121conH1 2x107.5 ml -1 Intramuscular 0, 21 DPV 3 9 ORFVΔ121conH1 2x107.5 ml -1 Intramuscular 0, 21 DPV 4 9 Sham – Intramuscular 0, 21 DPV 5 8 Sham – Intramuscular 0, 21 DPV Group Challenge Inoculum titer Route Challenge day 1 Mock (MEM) – Intranasal and intratracheal 40 DPV 2 OH/07 (gamma) 1x107.0/route Intranasal and intratracheal 40 DPV (npdm) 1x107.0/route Intranasal and intratracheal 40 DPV (npdm) 1x107.0/route Intranasal and intratracheal 40 DPV (gamma) 1x107.0/route Intranasal and intratracheal 40 DPV days post vaccination 85007-399822 -134- [00141] All immunizations were performed via intramuscular (IM) route by injection of 2 ml of a virus suspension containing 107.5 TCID50 ml-1 or 2 ml of MEM. Animals from Group 1, 4 and 5 were sham immunized with MEM. While animals from Groups 2 and 3 were immunized with ORFVΔ121conH1. All animals were immunized on day 0 and received a booster immunization on day 21 post vaccination (DPV). The pigs from Groups 2 and 5 were challenged with a virus suspension of the OH07 virus intranasal and intratracheal (1x107 TCID50 ml-1/route) on 40 DPV. Similarly, the pigs from Groups 3 and 4 were challenged with a virus suspension of the CA09 virus (1x107 TCID50 ml-1/route) intranasally and intratracheally on 40 DPV. [00142] Animals were monitored daily. Serum samples and nasal swabs were collected on days 0 and 21 post-vaccination (DPV0 and DPV21) and days 0, 2, 4, and 6 post-challenge (DPC0, DPC2, DPC4 and DPC6). All animals were handled in accordance with the Animal Welfare Act and the animal immunization challenge studies were conducted at The Ohio State University (OSU), following the guidelines and protocols approved by the Institutional Animal Care and Use Committee (IACUC approval no. 2017R00000016). Humoral responses against divergent IAV-S viruses [00143] IAV-S-specific IgG immune responses elicited by immunization with ORFVΔ121conH1 were assessed by whole virus ELISA of serum and bronchoalveolar lavage, respectively. A panel of 12 WIV antigens for IgG-ELISA were prepared as described previously with some modifications. Briefly, ultra-centrifugation on 30% sucrose cushion gradient of virus culture supernatant was performed using Optima-L 100K ultracentrifuge (Beckman Coulter) at 17,000 RPM for 1.5 hours. The virus pellet was resuspended in DMEM and heat inactivation of the virus was carried out using a water bath placed at 56°C for 30 min. Determination of the optimal coating antigen concentration and dilution of secondary antibodies were performed by checkerboard titration. 85007-399822 -135- [00144] To detect IAV-S specific total IgG, Immulon 1B ELISA plates (ThermoFisher Scientific, catalog no: 3355) were coated with 250 ng/well in 100 μL volume of concentrated and heat-inactivated panel of IAV-S virus in bicarbonate/carbonate coating buffer (15 mM sodium carbonate, 35 mM sodium bicarbonate, pH 9.6) in duplicate wells. After 1.5h incubation at 37°C, plates were washed three times with PBS-T (1X PBS with 0.5% Tween-20) and blocked overnight with 200 μL/well of blocking solution (5% milk in PBS-T) at 4°C. Blocking reagent was removed and plates washed three times with PBS-T. Test and control serum samples were diluted (1:50) in PBS-T 5% non-fat dry milk, and 100 µl of diluted samples were added to paired coated and uncoated control wells and incubated at RT for 1 h. Unbound antibodies were washed with PBS-T (3 times) and plates were incubated with biotinylated secondary antibodies against swine IgG (Bethyl Laboratories, catalog no: A100-104, TX) diluted in blocking buffer (1:4000) for 1 hr at RT, followed by washing (3 times) and incubation with streptavidin-HRP conjugate (Thermo Scientific , catalog no: 21136, Pierce, Rockford, IL) diluted in blocking solution (1:4000) for 1 hr at RT. Streptavidin-HRP conjugate reactions were developed with 3,3’,5,5’- tetramethylbenzidine substrate (TMB) (KPL, catalog no: 5120-0047, Gaithersburg, MA). Finally, the colorimetric reaction was stopped by adding 100 μL 1N HCl solution per well. Optical density (OD) values were measured at 450 nm using a microplate reader (Tecan, Mannedorf, Switzerland). OD values for each test and control samples were normalized to the OD value of uncoated. All assay formats were pre-optimized using serum samples from animals of known serological status. Virus titration [00145] Infectious IAV-S titers in the swabs and tissue samples were determined by the Spearman and Karber's method and expressed as tissue culture infections dose 50 (TCID50) per ml. Briefly, ten-fold serial dilutions of the samples were transferred to a 96- well plate pre-seeded with MDCK cells 24 h earlier and incubated at 37°C for 1 hour. After 1 hour of adsorption, the inoculum was removed and fresh DMEM containing 2 μg 85007-399822 -136- ml -1 of TPCK-treated trypsin was added to the cells. After 48-hour incubation at 37°C, cells were fixed with 3.7% formaldehyde, washed three times with PBS and permeabilized with 0.2% PBS-Triton X-100 for 10 min at RT. Virus positive MDCK cells were detected by immunofluorescence assay using a 1:500 of a mouse monoclonal antibody (mAb) targeting conserved nucleoprotein (NP) of influenza virus (IAV-NP HB- 65462 mAb; kindly provided by Drs. Eric Nelson and Steve Lawson at SDSU), followed by incubation with Goat Anti-Mouse IgG Monoclonal Antibody DyLight® 488 (Bethyl Laboratories Inc., Montgomery, TX) at 1:350 as described in “Immunofluorescence” from this section. The viral titer was defined as the reciprocal of the highest dilution of the virus where there was infection/replication as evidenced by presence of fluorescent foci. Appropriate positive and negative control samples were included in all the plates. Real-time reverse transcriptase PCR (rRT-PCR) [00146] Virus shedding in nasal secretions and viral load in lungs was evaluated by rRT-PCR. Viral nucleic acid was extracted from the nasal swabs and lung tissue homogenates. The lung tissue from the euthanized pigs was collected and lung lysates were prepared in DMEM without serum. Approximately 2–5 g of lung tissue of individual pigs was minced and homogenized for 2 min in a Stomacher 400 laboratory blender (Seward, Long Island, NY), clarified by centrifugation, and the supernatant was collected, aliquoted and frozen at -80°C until usage. All RNA extractions were performed at using the MagMax Core extraction kit (Thermo Fisher, Waltham, MA, USA) and the automated KingFisher Flex nucleic acid extractor (Thermo Fisher, Waltham, MA, USA) following the manufacturer’s recommendations. The presence of IAV-S RNA was assessed using RNA- to- Ct 1 Step- kit (Applied Biosystems) and custom designed primers and probe (Prime- Time qPCR probe assays, Integrated DNA Technologies, USA) targeting the conserved NP gene. Amplification and detection were performed using the CFX96 Touch Real-Time PCR Detection System (Bio- Rad), under following conditions: 10 min at 48ºC for reverse transcription, 10 min at 95 °C for polymerase activation and 40 cycles of 15 s at 95 °C for denaturation and 60 s at 60 °C or annealing 85007-399822 -137- and extension. A standard curve was established by using ten-fold serial dilutions from 10−1 to 10−8 of either OH/07 or CA/09 virus suspension containing 105.25 TCID50 ml -1 and 105.38 TCID50 ml -1, respectively. Relative viral genome copy numbers were calculated based on the standard curve derived from four-parameter logistic regression analysis and determined using the CFX Maestro software (Bio-Rad) as log10 genome copy numbers ml -1. Positive and negative amplification controls were run side by side with test samples. Cellular immune responses [00147] On the day of the necropsy (DPC6), heparinized blood was collected for isolation of peripheral blood mononuclear cells (PBMCs), also collected bronchoalveolar lavage (BAL) and tracheobronchial lymph nodes (TBLN) tissues for isolation of mononuclear cells (MNCs). The frequency of T-cell subsets secreting IFN-γ and IL-17A following recall stimulation with 0.1 MOI of A/Swine/OH/24366/2007 or A/California/04/2009, depending on the challenge virus used for group, was measured using intracellular cytokine staining (ICS) flow cytometry assay as previously described. Briefly, 5 million cells were seeded per well in a 48-well flat bottom plate in 1 ml of culture medium (RPMI 164010% FBS) in the presence of recombinant porcine IL-2 and OH/07 or CA/09 (0.1 multiplicity of infection-MOI) for 48 hours (hrs) in vitro. For the last 6 h of the incubation period, protein transport inhibitor Brefeldin A (GolgiPlug) was added. At the end of incubation, cells were harvested, washed, blocked with 1% normal rabbit serum, and separated into appropriate number of wells in a 96-well round bottom plate for surface and intracellular cytokine labeling. Appropriate isotype control antibodies were included as negative controls. For FACS panels with purified/unlabeled monoclonal antibody (mAb), the cells were first labeled with purified mAb and its corresponding secondary antibody followed by blocking with 1% normal mouse serum. This step was followed by labeling with other cell markers together as a cocktail. Cells were transferred to a 96-well round bottom plate, washed twice in 200 µl FACS buffer/well, and subjected to surface labeling using fluorochrome conjugated mAbs 85007-399822 -138- against indicated markers and their corresponding isotype controls at pre-titrated concentrations in 50 µl of FACS buffer for 30 min at 4oC. Cells were then fixed using 1% paraformaldehyde at 4oC for 30 min and resuspended in 200 µl FACS buffer. [00148] For intracellular labeling, cells were washed once and permeabilized with 1% saponin for 45 min at room temperature. Subsequently, cells were washed with saponin wash buffer (0.1% saponin) and incubated with fluorochrome conjugated mAbs against indicated markers and their corresponding isotype controls using pre-titrated concentrations in 50 µl final volume in saponin wash containing 1% normal rabbit serum for 45 min at 4oC. Cells were washed once in saponin wash and labeled with indicated secondary antibodies for 45 min at 4oC. Cells were washed once and resuspended in 200 µl FACS buffer and transferred to FACS tubes and analyzed using a live cell gate in a BD FACS Aria II flow cytometer. For each sample, 100,000 events were acquired. The data were analyzed using FlowJo software (FlowJo V10, Becton, Dickinson& Company; BD) and plotted using GraphPad Prism (GraphPad Prism 9, CA). [00149] Cells were immunostained for T-helper/memory cells (CD3+CD4+CD8α+β-) and cytotoxic T lymphocytes (CTLs) (CD3+CD4+CD8α+β+) using specific immune markers, including purified or fluorochrome labeled antibodies anti-porcine CD3 (Southern biotech, AL), CD4α (Southern biotech, AL), CD8α (Southern biotech, AL), CD8β chain (BD Pharmingen, CA), IFN-γ and IL-17A, and their corresponding isotype controls at previously titrated and optimized concentrations. Positive and negative populations, quadrant markers were set, and these were controlled by non-stained samples and samples incubated only with isotype control antibodies. Lymphocyte subpopulations were separated initially by CD3+ and CD3- gates. The frequency of each individual type of lymphocyte was expressed as the frequency (percentage) of these cells within the 100,000 cells counted. EXAMPLE 2 Generation and Characterization of the ORFVΔ121conH1recombinant virus 85007-399822 -139- [00150] Phylogenetic analyses based on the nucleotide sequence displays the designed conH1 in the center of the phylogenetic tree (Figure 1A). The genetic distance between conH1 was dramatically reduced in comparison with the HA sequences from recent circulating strains from H1 subtype used for the in silico design of conH1 (Figure 1B). The full-length consensus H1 protein of IAV-S was inserted into the gene locus 121 of the ORFV genome (ORFV121) by homologous recombination (Figure 1C). After deletion and purification, deleted ORFV121 gene sequences were not detected in the purified recombinant virus (Figure 1D), while conH1 sequences were detected in the recombinant virus but not in the wild-type ORFV genome (Figure 1E). The presence of conH1 and efficient processing and cleavage of conH1 HA0 into HA1 and HA2 subunits were detected in ORFVΔ121conH1-infected cells by Western blot (WB) assay (Figure 1F). Complete genome sequence of the ORFVΔ121conH1 recombinant virus confirmed the insertion of the full-length conH1 sequence of IAV-S, the integrity of ORFV genome and complete deletion of the virulence determinant ORFV121 (data not shown). [00151] Replication properties of the ORFVΔ121conH1 were similar to the wild- type (WT) virus (OV IA82) in OFTu cells (Figure 2A). In contrast, a marked growth defect for both WT OV-IA82 and ORFVΔ121conH1 was observed in primary STu cells (Figure 2B), indicating minimal or no virus replication in cells of porcine origin, as previously found in other studies. EXAMPLE 3 Recombinant ORFVΔ121conH1 expresses conH1 in vitro [00152] Expression of conH1 by ORFVΔ121conH1recombinant virus was assessed by immunofluorescence (IFA) and flow cytometry assays. Expression of conH1 by the recombinant ORFVΔ121conH1 was assessed during virus infection in OFTu cells by using an anti-Flag mAb using IFA and flow cytometry assays. Importantly, these studies indicate expression of conH1 intracellularly, as showed by the intense fluorescence in permeabilized cells, and on the surface of infected cells, as showed by immunofluorescence staining in non-permeabilized ORFVΔ121conH1-infected cells 85007-399822 -140- (Figures 3A and 3B). Additionally, IFA assays performed in infected cells performed with serially passaged ORFVΔ121conH1 showed stable expression of the full-length of the inserted conH1 by the recombinant virus on passages 1, 5 and 10. Together, these results demonstrate robust expression of conH1 in cells infected with the recombinant ORFVΔ121conH1 virus. EXAMPLE 4 Cross-reactivity between H1N1 porcine antisera and the conH1 in vitro [00153] The ability of antibodies present in porcine antisera induced by infection with divergent H1N1 strains to recognize B cell epitopes in the conH1 was studied. Three different antisera from H1N1 strains isolated between 2005-2009 representing different IAV-S clades that circulates in the U.S. were used in this assay: anti- A/California/04/2009 (H1N1) belonging to the pandemic clade, -A/swine/IL/00685/2005 (H1N1) from clade delta2, and -A/swine/Kentucky/02086/2008 (H1N1) from clade beta. Cross-reactivity and antibody binding to the conH1 was observed with all three antisera, suggesting that the conH1 expressed by the recombinant ORFVΔ121conH1 virus was recognized by antibodies present in the sera of swine infected by divergent H1N1 viruses (Figure 4A). Alignment of the conH1 amino acid sequences with the HA proteins of these cross-reactive viruses was performed to evaluate genetic relationship between these viruses (Figure 4B and 4C). The conH1 sequence used to construct ORFVΔ121conH1 possessed the lowest amino acid difference (12.4%) with the HA sequence of the virus A/swine/IL/00685/2005 (H1N1). However, the higher cross-reactivity was found using the A/California/04/2009 (86.2% pairwise identity) and A/swine/Kentucky/02086/2008 (84.2% pairwise identity) sera. EXAMPLE 5 ORFVΔ121conH1 recombinant virus elicited humoral immune response in pigs [00154] At DPC0, IAV-S-specific total IgG antibodies were significantly higher in the immunized when the whole virus ELISA was performed using the challenge virus 85007-399822 -141- antigen (Figures 5A and 5B). The breadth of IAV-S IgG immune response induced by ORFVΔ121conH1 at DPC0 was also explored against a panel of 10 divergent viruses by whole virus ELISA (Table 2). At DPC0, within the group of animals that were further challenged with OH/07, the immunized group showed a significant increase of total IgG levels in serum using A/Swine/South Dakota/A02524887/2020 whole virus as an antigen. Similar to OH/07, A/Swine/South Dakota/A02524887/2020 virus also belongs to the U.S. H1N1 clade gamma, referred as classical swine lineage worldwide. Notably, the nucleotide identity between the HA of conH1 used to generate the recombinant virus and the HA of A/Swine/South Dakota/A02524887/2020 is 88.1%, and in the amino acid level, the similarity was 89.1% (Table 2). Within the panel of viruses used for the whole virus ELISA, these numbers show the HA of A/Swine/South Dakota/A02524887/2020 share the second highest homology with the HA of conH1, after only OH/07, with a pairwise identity of 89.2% and 89.8%, respectively (Table 2). On the other hand, within the animals challenged with CA/09, the vaccinated group showed a significantly increased total IgG levels on DPC0 against A/Swine/South Dakota/A02524887/2020 (clade gamma), A/Swine/Michigan/A02524810/2020 (clade npdm), A/Swine/Texas/A02245632/2020 (beta clade), A/Swine/Oklahoma/A02245707/2020 (clade beta), and A/Swine/Oklahoma/A02214419/2017 (clade delta 1). Interestingly, these five viruses belong to different H1N1 clades, with amino acid homology ranging between 83 and 89% (Table 2). At DPC6 no difference was found between unvaccinated and vaccinated using the challenge viruses as antigens. Within the groups challenged with OH/07 (clade gamma), the vaccinated group maintained the significant increase of total IgG levels using A/Swine/South Dakota/A02524887/2020 (clade gamma) whole virus as an antigen. In addition, increased levels of total IgG antibodies were detected against A/Swine/Michigan/A02524810/2020 (clade npdm), which the HA sequence has 84.3 and 85.3% of identity for nucleotides and amino acids, respectively (Table 2). Also, within the groups challenged with CA/09 (clade npdm), the vaccinated group continued to present increased IgG with A/Swine/South Dakota/A02524887/2020 (clade gamma), A/Swine/Michigan/A02524810/2020 (clade npdm)., 85007-399822 -142- A/Swine/Oklahoma/A02245707/2020 (clade beta), and A/Swine/Oklahoma/A02214419/2017 (clade delta 1) whole virus antigens. [00155] ORFVΔ121conH1 recombinant virus induced cellular immune response in pigs. T-cell responses elicited by immunization with ORFVΔ121conH1 virus were assessed on peripheral blood mononuclear cells (PBMCs), and mononuclear cells from bronchoalveolar lavage (BAL) and tracheobronchial lymph nodes (TBLN) at DPC6. The percentage of T- helper/memory cells (CD3+CD4+CD8α+β-) secreting IFN-gamma (IFNγ+) (Figure 6A and 6E) and IL-17 (IL17+) (Figure 6G) in PBMCs were significantly higher in the vaccinated groups. Similarly, IFNγ+ cytotoxic T lymphocytes (CTLs) were also enhanced in ORFVΔ121conH1-immunized groups compared to unvaccinated animals challenged with CA/09 (Figure 6G). Differences in percentage of IL17+ CTLs were only observed between immunized animals and the respective sham-immunized/mock challenged group (Figure 6D and 6H). [00156] In BAL, the percentage of T cells CD3+CD8α+CD8β+ secreting IL17A and IFN-γ induced upon stimulation were significant higher in the vaccinated compared to unvaccinated animals in the groups challenged with OH/07 at DPC6 (Figure 7A and 7B), but no difference was found for IFN-γ secreting cells in the groups that received the CA/09 challenge (Figure 7C and 7D). [00157] In the contrast, the levels of IL-17A+ and IFNγ+ secreting T cells CD3+CD8α+CD8β+ in TBLN MNC of swine vaccinated and challenged with CA/09 were significantly higher at DPC6 compared to sham-immunized pigs (Figure 8C and 8D), whereas no difference was found in the OH/07 challenged groups (Figure 8A and 8B). [00158] Virus shedding after intranasal IAV-S challenge. The protective efficacy of ORFVΔ121conH1 was evaluated upon challenge with OH/07 and CA/09. The 10-fold decrease in infectious virus present in nasal swabs of vaccinated groups compared to their respective sham-immunized group at DPC2 (Figure 9A and 9B) suggests early control of virus replication in immunized animals. Significant decrease (approximately 20-fold) in infectious virus and genome copy numbers was also observed at DPC6 in nasal swabs of 85007-399822 -143- vaccinated groups compared to their respective sham-immunized group (Figure 9A and 9B). These results demonstrate that immunization with ORFVΔ121conH1 resulted in decreased shedding of infectious virus and lower genome viral loads in nasal secretions following IAV-S challenge with diverse H1N1 challenge viruses. [00159] Macroscopic lesions in the lung were also evaluated. The lesion scores were significantly lower in ORFVΔ121conH1-immnunized group when compared to sham-immunized animals that were challenged with the same CA/09 virus (Figure 10A). Finally, viral load was determined in the BAL of sham- and ORFVΔ121conH1-immunized pigs at DPC6 by genome copies ml -1 (log 10) and TCID50 ml -1. Despite the 10-fold lower load of IAV-S RNA detected in the BAL of vaccinated animals, there was no significant difference in terms of infectious virus titers between sham- and ORFVΔ121conH1-immunized groups (Figure 10B). Taken together, these results demonstrate that immunization with ORFVΔ121conH1 was able to reduce viral shedding after intranasal infection with divergent strains of IAV-S H1N1 (OH/07 and CA/09) and dimmish lung lesions upon infection with a pandemic virus isolate (CA/09). EXAMPLE 6 Material and Methods Cells and viruses [00160] Primary ovine fetal turbinate (OFTu), swine fetal turbinate (STu) and Madine Derby Canine Kidney (MDCK), were used for viral propagation and cell-based assays. The cells were cultured in Minimum Essential Medium (MEM), supplemented with 10% Fetal Bovine Serum (FBS, heat inactivated), 2 mM L-glutamine, and antibiotics (penicillin, streptomycin, and gentamicin). The wild-type ORFV (OV strain IA82) was provided by Dr. Daniel Rock at University of Illinois at Urbana-Champaign (7,30,31) and served as the parental virus to generate recombinant ORFV viruses that express heterologous HA proteins derived from avian (AIV, heads) and swine influenza virus (IAV-S, stalk). Both wild-type (wt) and recombinant Orf viruses were propagated in primary OFTu cells. 85007-399822 -144- [00161] Two H1N1 IAV-S strains, A/Swine/OH/24366/2007 (Oh07), from the gamma clade, and A/California/04/2009 (Ca09), from the "new pandemic" (npdm) clade, provided by Dr. Aradhya Gourapura at Ohio State University, and obtained from the National Veterinary Services Laboratory (NVSL) (Ames, Iowa), respectively, were used to evaluate the efficacy of the recombinant vaccine candidates. Amplification of IAV-S was performed in MDCK cells using DMEM supplemented with HEPES buffer and TPCK-treated trypsin at a concentration of 2 µg/mL. Subsequently, these viruses were utilized for virus challenge and antigen preparation for the whole virus ELISAs. [00162] For the whole virus IgG ELISA, a panel of ten additional IAV-S isolates was acquired from NVSL to comprise representativesviruses of all H1 circulating clades. These isolates are listed in Table 5. Table 5. Panel of the 12 IAV-S belonging to the H1 subtype used in different assays throughout this study Info Ohio/07 California/09 Iowa/20 85007-399822 -145- Year 2020 2017 2020 Clade npdm delta 1 beta Info South Dakota/18 South Dakota/20 Texas/20 Construction of recombinant cassettes. [00163] To generate the two recombinant ORFV-SIV viruses evaluated in this study, chimeric-HA (cHA) coding sequences were designed in silico and chemically synthesized and cloned into the pUC57 plasmid (GenScript®, Piscataway, NJ). Briefly, the cHAs were designed based on the stalk domain (nucleotide residue 1033 to 1698) of a contemporary H1N1 IAV-S strain [(A/swine/Minnesota/A02245569/2020 (H1N1) GenBank access MT372532], and exotic head domains selected to avoid IAV subtypes found in swine (H1 and H3) and those associated with HPAI (H5 and H7). The head domain of the cHAs used in this study was based either in an avian Influenza A virus (AIV) belonging to the H6 subtype [(A/American Green-winged Teal/Ohio/18OS2656/2018(H6N1) GenBank access MN430905.1] or the H8 subtype [(A/Mallard/Ohio/18OS1248/2018(H8N4) GenBank access MN431074.1] (Figure 11B). For the design of the chimeric-HAs, cH6/1 and cH8/1, restriction endonuclease sites required for DNA insertion into the ORFV121 locus of the ORFV genome were added, whereas HindIII and SalI were added to the N- and C-terminus of cH6/1, SpeI and SalI were added to the N- and C-terminus of cH8/1. The Flag-tag epitope was added to the 3' end, and either the p116 , an early/late ORFV internal promoter, or the vaccinia virus late 85007-399822 -146- I1L promoter, were added to the 5’ end of the coding sequence of cH6/1 and cH8/1, respectively. Finally, any potential transcription termination nucleotide sequences, including the TTTTTNT poxviral transcription termination signal, were removed from the chimeric HA coding sequence through silent nucleotide substitutions. The resulting synthesized DNA fragments were subcloned into the poxviral transfer vector pUC57- ORFVΔ121loxP-EGFP, resulting in two recombinant cassettes, pUC57-ORFVΔ121cH6/1- loxP-EGFP and pUC57-ORFVΔ121cH8/1-loxP-EGFP. Correct cloning was confirmed by restriction enzyme, followed by indirect immunofluorescence assay (IFA) of transfected cells using a Flag-tag mouse monoclonal antibody (Thermo Fisher Scientific, Waltham, MA). Generation of recombinant ORFVΔ121cH6/1 and ORFVΔ121cH8/1-IAV-S. [00164] To generate the recombinant ORFVΔ121cH6/1 and ORFVΔ121cH8/1-IAV-S viruses, the full-length sequences of cH6/1 and cH8/1 were inserted into the ORFV121 locus through homologous recombination between the wt OV IA82 and the recombination plasmids pUC57-ORFVΔ121cH6/1-loxP-EGFP and pUC57- ORFVΔ121cH8/1-loxP-EGFP (Figure 11C and 11D) using Lipofectamine 3000 (Life Technologies, Carlsbad, CA), as described by Joshi et al. 2021. The presence of the chimeric HAs and the absence of the wild-type virus was confirmed by PCR amplicon electrophoresis analysis in 1% agarose gel using two pairs of primers designed for the PCR amplification of the stalk domain of H1, and an internal region of ORFV121 (401 bp), respectively. The primers for the stalk domain of the chimeric-HAs were Fw-5’- ACTGCGGTACCTATTTAAAAGTTGTTTGGTGAACTTAAATGGG- CCTATTCGGGGCCATTGC-3’ (SEQ ID. NO: 17) and Rv-5’- GAGGTCTCGAGTTACTTGTCGTCATCGTCTTTG-TAGTCAATCT- GGTAGATCTTTGTTGAGTCCAGC-3’ (SEQ ID. NO: 18) (637 bp), while the primers for the ORFV121 (401 bp) were previously described. PCR was performed using Q5® Hot Start High-Fidelity DNA Polymerase, following the recommendations from the manufacturer. For each reaction, specific annealing temperatures were utilized based on 85007-399822 -147- the optimal melting temperature (Tm) of the primers used (62°C for amplifying the cHA1 stalk fragment and 56.5°C for amplifying a fragment of the ORF121 locus). To validate the presence and integrity of the heterologous genes and ensure the preservation of OV IA82 identity and integrity with the deletion of the ORFV121, whole genome sequencing was performed using the MinION Mk1B sequencing platform (Oxford Nanopore Technologies, ONT). In vitro characterization of ORFVΔ121cH6/1 and ORFVΔ121cH8/1-IAV-S. [00165] Replication kinetics of ORFVΔ121cH6/1 or ORFVΔ121cH8/1-IAV-S recombinant viruses were assessed through single- and multi-step growth curves in OFTu and STu cells and compared to the parental OV-IA82, as previously described. [00166] To evaluate the expression of heterologous genes by the recombinant viruses, OFTu cells were infected with either ORFVΔ121cH6/1 or ORFVΔ121cH8/1-IAV-S, and assessed by indirect immunofluorescence assay (IFA), flow cytometry and Western Blot, as previously described. [00167] The stability of both cH6/1 and cH8/1s gene inserted into the ORFV121 locus was evaluated during 10 serial passages of the respective recombinant virus in OFTu cells by assessing expression through IFA, as previously described. Immunization-Challenge study in swine. [00168] The ability of ORFVΔ121cH6/1 or ORFVΔ121cH8/1-IAV-S to induce immune responses and protection was evaluated in pigs. A total of forty-two 3-week-old pigs, seronegative for IAV, were randomly assigned to four experimental groups as follows: Group 1 - ORFVΔ121cH6/1 (prime) + ORFVΔ121cH8/1-IAV-S (boost) immunized/Oh07 challenged (n = 7); Group 2, ORFVΔ121cH6/1 (prime) + ORFVΔ121cH8/1-IAV-S (boost) immunized/Ca09 challenged (n = 7), Group 3, sham- immunized/Oh07 challenged (n = 7), and Group 4 sham-immunized/Ca09 challenged (n = 7). 85007-399822 -148- [00169] Immunizations were performed by intramuscular injection of either 2 ml of a virus suspension containing 107.38 TCID50 ml-1or (Groups 1 and 2) or 2 ml of MEM (Groups 3 and 4). Animals were immunized on day 0 (D0) and boosted on day 21 (D21). Two divergent viruses were selected for the challenge: Sw/OH/24366/2007 (H1N1) (Oh07) and A/California/04/2009 (H1N1) (Ca09). On day 35 (D35), pigs in groups 1 and 3 were challenged intranasally with a virus suspension containing 1x107 TCID50 ml-1 of IAV-S Oh07, while groups 2 and 4 received an intranasal challenge with 1x107 TCID50 ml-1virus suspension of IAV-S CA09. [00170] Throughout the study, animals were monitored daily for clinical signs of influenza infection. Serum and whole blood samples were collected on days 0, 21, 28, and 35 post-immunization (D0, D21, D28, and D35), as well as on days 3, 5, and 7 post- challenge (DPC3, DPC5, and DPC7). Nasal swabs were collected at DPC0, DPC3, DPC5, and DPC7. The animal study was conducted at Cornell University, adhering to the guidelines and protocols approved by the Institutional Animal Care and Use Committee (IACUC approval no. 2019-0041) and in accordance with the Animal Welfare Act Amendments. Antibody isotype ELISAs. [00171] Levels of specific IgG antibodies in sera and IgA antibodies in the bronchoalveolar lavage (BAL) were determined by whole virus ELISA against 12 distinct IAV-S, following previously described methods, with some modifications. gG (Bethyl Laboratories, catalog no: A100-104, TX). Specifically, Immulon 1B ELISA plates (Thermo Fisher Scientific, catalog no: 3355) were coated with 500 ng/well of concentrated and heat-inactivated viruses instead of 250 ng and incubated them with the according goat anti-pig biotinylated antibody IgG or IgA (Bethyl Laboratories, catalog no: A100-104, or A100-102A, respectively, TX) at diluted at 1:2000 instead of 1:4000 in 5% non-fat milk Tris-buffered saline (PBS) with 0.05% Tween 20 detergent (PBST). [00172] The serum samples were evaluated by measuring their optical density (OD) at 450 nm using a microplate reader (SYNERGY LX, BioTek, Winooski, VT, 85007-399822 -149- USA). To standardize the OD values, each test and control sample was compared to the OD value of an uncoated well. Prior to the actual testing, all assay formats were optimized using serum samples from animals with known serological status. Viral load and infectious virus in nasal secretions and tissues. [00173] Viral load in nasal secretions, bronchoalveolar lavage (BAL) and lungs was determined by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Lung lysates for RNA extraction were prepared with 2 g of lung tissue of individual pigs which were homogenized in 20 mL MEM. Approximately 200 µl of the tissue homogenate supernatant were subjected to nucleic acid extraction using the MagMax Core extraction kit (Thermo Fisher, Waltham, MA, USA) and the KingFisher flex automated extraction platform as previously described. Real-time RT-PCR using Path- ID™ Multiplex One-Step RT-PCR kit (Thermo Fisher, Waltham, MA, USA), targeting the conserved matrix (M) gene (Integrated DNA Technologies; Coralville, IA, USA) were used to detect RNA from influenza A virus. The probe, and forward and reverse primers used were 5’-FAM-TCA GGC CCC CTC AAA GCC GA-BHQ1 -3′ (SEQ ID. NO: 19), 5′- AGA TGA GTC TTC TAA CCG AGG TCG -3′ (SEQ ID. NO: 20), and 5′- TGC AAA AAC ATC TTC AAG TCT CTG -3′ (SEQ ID. NO: 21), respectively. The cycling conditions for amplification of the M gene target were 10 min at 48ºC for reverse transcription, 10 min at 95ºC for polymerase activation, 45 cycles of 15 s at 95ºC for denaturation and 1 min at 60ºC for annealing and extension, performed using the CFX96 Touch Real-Time PCR Detection System (Bio- Rad). Standard curves were established using ten-fold serial dilutions ranging from 10−1 to 10−8 of either Oh07 or Ca09 virus stocks. The genome copy numbers mL-1 (log10) of each sample was derived from the CTs obtained for the established standard curves by CFX Maestro software (Bio-Rad), as previously described. Appropriate positive and negative controls were added to each extraction and PCR plates to be run along with test samples. [00174] Additionally, infectious virus in nasal swabs and tissue samples was assessed in MDCK cells and expressed as TCID50 mL-1, as described in previous studies. 85007-399822 -150- The mouse monoclonal antibody (mAb) used for the viral titration by IFA was provided by Drs. Eric Nelson and Steve Lawson at SDSU (IAV-NP HB-65462 mAb; at 1:500). This antibody targes the conserved nucleoprotein (NP) of influenza A viruses. The presence of fluorescent foci indicated virus-positive wells. Statistical analysis. [00175] Graphpad Prism software v9.0 (GraphPad Software, San Diego, CA, USA) was used for all statistical analyses. Shapiro–Wilk test was performed to verify data’s normality, followed by either t-test or unpaired t-test to compare means between the groups for either normal, or non-normal data, respectively. Tukey multiple comparison post-test was performed for pairwise comparison. P value lower than 0.05 was considered significant. The flow cytometry data was acquired using the Attune NxT Flow Cytometer and analyzed with FlowJo software (FlowJo V10, Becton, Dickinson & Company; BD, Franklin Lakes, NJ, USA). EXAMPLE 7 In vitro expression of the heterologous proteins by ORFVΔ121cH6/1 and ORFVΔ121cH8/1 viruses [00176] The expression of cH6/1 and cH8/1 by the respective recombinant viruses were verified through IFA, WB, and flow cytometry by using an anti-FLAG mAb. The red fluorescence in ORFVΔ121cH6/1 (Figure 12A) and ORFVΔ121cH8/1 (Figure 12B) infected cells was observed inside the cells (permeabilized) and on their surface (unpermeabilized). Notably, the levels of the chimeric HA proteins (~70 kDa), detected through the flag epitope, increased up to 72 hpi in ovine cells infected at 10 MOI by the recombinant ORFVΔ121cH6/1 (Figure 12C) and ORFVΔ121cH8/1 (Figure 12D). The flow cytometry data reinforced the findings from IFA and WB assays (Figure 12E and 12F). [00177] Additionally, expression of cH6/1 and cH8/1 were also assessed by flow cytometry at 72 hpi. Expression of cH6/1 and cH8/1 by the recombinant ORFVΔ121cH6/1 85007-399822 -151- and ORFVΔ121cH8/1 viruses were observed in approximately 56 % and 47% of the cells intracellularly and in 31% and 25% of the on the plasma membrane of infected cells, respectively. [00178] PCR amplification (Figure 13A) and whole genome sequence confirmed the integrity of the inserted chimeric HA sequences in the ORFVΔ121cH6/1 and ORFVΔ121cH8/1 viruses. Replication kinetics of ORFVΔ121cH6/1 and ORFVΔ121cH8/1- IAV-S were assessed in OFTu and STu cells by multi- and single-step growth curves (Figure 13B). Both viruses replicated to high titers in OFTu cells, while as expected a markedly impaired replication was observed in primary swine cells. EXAMPLE 8 Humoral immune response in swine [00179] IAV-S-specific total IgG antibodies were detected as early as 3 weeks post prime-vaccination and increased markedly after the booster immunization on D21 continuing to raise until D42 (7dpc) in animals that received the sequential immunization with ORFVΔ121cH6/1 as priming and ORFVΔ121cH8/1-IAV-S as booster (OV- cH6/1- cH8/1) against both challenge viruses (Figure 14A). Similar results were detected using either Oh07 or Ca09 purified viruses as antigen for the ELISA (Figure 14B). An anamnestic response was observed in both groups following the challenge infection with both Oh07 and CA09 viruses. Notably, IgG levels reached their peak at D42 (or DPC7), suggesting that IgG memory B cells generated post immunizations were activated upon experimental challenge infection. [00180] The breadth of IAV-S specific IgG immune response induced by vaccination was also assessed against a panel of 10 divergent viruses on D35 (DPC0) (Table 5). The animals that received the prime and booster with the recombinant ORFVΔ121cH6/1 and ORFVΔ121cH8/1 viruses presented significantly higher IgG responses (Figures 15A and 15B). These results demonstrate a broad binding capability of the antibodies elicited by IM immunization of the chimeric viruses in pigs. 85007-399822 -152- EXAMPLE 9 Mucosal immunity in lungs [00181] The mucosal antibody responses in vaccinated compared to sham- immunized pigs were assessed measuring the IgA antibody levels in BAL post euthanasia at D42 against the same panel of divergent viruses used in previous ELISA assays. [00182] The immunized animals within the OH07 challenge groups presented significant higher levels of IgA against all the 12 IAV-S viruses compared to the sham- immunized swine (Figure 16A). On the other hand, vaccinated swine challenged with the CA09 virus showed significantly higher IgA responses for all divergent viruses except SD/18, Missouri/20, and Oh/07, which belongs to gamma-2-beta-like, npdm and gamma clades, respectively (Figure 16B). These findings suggest cross-reactive mucosal immune responses were elicited by IM immunization with the recombinant ORFVΔ121cH6/1 and ORFVΔ121cH8/1 viruses in swine. EXAMPLE 10 Viral shedding in nasal swabs [00183] The presence of viral RNA and infectious virus in nasal secretions was assessed after intranasal challenge with either Oh07 or Ca09 viruses. Animals immunized with OV-cH6/1-cH8/1, and subsequently challenged with Oh07 showed approximately 10-fold decrease in infectious virus shedding through nasal secretions on DPC1, and this difference reached 20-fold at DPC5, compared to the respective sham-immunized group (Figure 17A). Similar results were observed in viral RNA load as determined by RT- qPCR. The peak virus shedding for the OV-cH6/1-cH8/1+Oh07 challenged pigs was DPC3, showing no significant increase in infectious virus and genome copy numbers from DPC1 to DPC3. Taken together, these findings suggest an early control of Oh07 replication, and early viral clearance in immunized animals. In contrast, no difference was found in the Ca09 challenged groups besides a slightly decrease in the viral RNA in the vaccinated group at DPC5 (Figure 17B). For both challenges, no infectious virus or IAV-S genome copies were found at DPC7 in any group. These results demonstrated that 85007-399822 -153- vaccination with OV-cH6/1-cH8/1 led to a decrease in viral shedding in nasal secretions after Oh07 infection, but not Ca09. EXAMPLE 11 Local lesions and viral load Macroscopic lesions presented in lungs were scored based on the method developed by Madec and Kobisch. Tissue consolidation represented by darker patchy areas were more pronounced in sham-immunized animals (Figure 19A-19D). Lesion scores were significantly lower in OV-cH6/1-cH8/1 immunized groups independently of the challenge virus (Figure 18A and 18B). Lesion scores were approximately ten-fold higher in the sham-immunized+Oh07 challenged animals, likely due to the higher pathogenicity of this virus strain in swine. Additionally, viral load in lung lysates and BAL were determined at D42 (DPC7) and expressed in genome copies mL−1 (log 10). Viral load in both lungs and BAL were 10-fold lower in vaccinated animals (Figure 18B). In summary, these results indicate that immunization with ORFVΔ121cH6/1- ORFVΔ121cH8/1-IAV-S was able to reduce viral loads and lung lesions.

Claims

85007-399822 -154- CLAIMS 1. An amino acid sequence comprising a consensus H1 hemagglutinin polypeptide. 2. The amino acid sequence of claim 1, wherein the consensus H1 hemagglutinin polypeptide comprises SEQ ID NO: 1. 3. The amino acid sequence of claim 1, wherein the consensus H1 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 1. 4. The amino acid sequence of claim 1, wherein the consensus H1 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 1. 5. A nucleotide sequence comprising a nucleic acid sequence encoding a consensus H1 hemagglutinin polypeptide. 6. The nucleotide sequence of claim 5, wherein the nucleic acid sequence comprises SEQ ID NO: 2. 7. The nucleotide sequence of claim 5, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 2. 8. The nucleotide sequence of claim 5, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 2. 9. A composition comprising a consensus H1 hemagglutinin polypeptide and a vector. 10. The composition of claim 9, wherein the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence comprising SEQ ID NO: 1. 11. The composition of claim 9, wherein the vector is a viral vector. 12. The composition of claim 11, wherein the viral vector is an ORFV vector. 13. The composition of claim 9, wherein the vector is a nucleic acid vector. 85007-399822 -155- 14. A pharmaceutical composition comprising i) a consensus H1 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers. 15. The pharmaceutical composition of claim 14, wherein the consensus H1 hemagglutinin polypeptide is comprised in the composition of any one of claims 9 to 13. 16. The pharmaceutical composition of claim 14, wherein the consensus H1 hemagglutinin polypeptide comprises an amino acid sequence comprising SEQ ID NO: 1. 17. The pharmaceutical composition of claim 14, wherein the pharmaceutical composition is formulated as a vaccine. 18. A method for inducing an immune response in an animal against an influenza A virus (IAV), the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of claims 14 to 17. 19. The method of claim 18, wherein the immune response comprises a Cytotoxic T lymphocyte (CTL) response. 20. The method of claim 18, wherein the immune response comprises an IgG response. 21. The method of claim 18, wherein the immune response comprises a T cell response. 22. The method of claim 18, wherein the immune response comprises a T-helper/memory cell response. 23. The method of claim 18, wherein the immune response comprises an IFN-γ response. 24. The method of claim 18, wherein the administration is a prophylactic administration to the animal. 25. The method of claim 18, wherein the animal is a porcine. 26. The method of claim 18, wherein the method comprises a reduction in IAV viral load of the animal. 85007-399822 -156- 27. The method of claim 18, wherein the method comprises a reduction in IAV virus shedding by the animal. 28. A method of preventing an influenza A virus (IAV) infection in an animal, the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of claims 14 to 17. 29. The method of claim 28, wherein the administration is a prophylactic administration to the animal. 30. The method of claim 28, wherein the animal is a porcine. 31. The method of claim 28, wherein the method comprises a reduction in IAV viral load of the animal. 32. The method of claim 28, wherein the method comprises a reduction in IAV virus shedding by the animal. 33. An amino acid sequence comprising a consensus H3 hemagglutinin polypeptide. 34. The amino acid sequence of claim 33, wherein the consensus H3 hemagglutinin polypeptide comprises SEQ ID NO: 3. 35. The amino acid sequence of claim 33, wherein the consensus H3 hemagglutinin polypeptide comprises at least 90% sequence identity to the sequence of SEQ ID NO: 3. 36. The amino acid sequence of claim 33, wherein the consensus H3 hemagglutinin polypeptide comprises at least 95% sequence identity to the sequence of SEQ ID NO: 3. 37. A nucleotide sequence comprising a nucleic acid sequence encoding a consensus H3 hemagglutinin polypeptide. 38. The nucleotide sequence of claim 37, wherein the nucleic acid sequence comprises SEQ ID NO: 4. 39. The nucleotide sequence of claim 37, wherein the nucleic acid sequence comprises at least 90% sequence identity to the sequence of SEQ ID NO: 4. 85007-399822 -157- 40. The nucleotide sequence of claim 37, wherein the nucleic acid sequence comprises at least 95% sequence identity to the sequence of SEQ ID NO: 4. 41. A composition comprising a consensus H3 hemagglutinin polypeptide and a vector. 42. The composition of claim 41, wherein the consensus H3 hemagglutinin polypeptide comprises an amino acid sequence comprising SEQ ID NO: 3. 43. The composition of claim 41, wherein the vector is a viral vector. 44. The composition of claim 43, wherein the viral vector is an ORFV vector. 45. The composition of claim 41, wherein the vector is a nucleic acid vector. 46. A pharmaceutical composition comprising i) a consensus H3 hemagglutinin polypeptide and ii) one or more pharmaceutically acceptable carriers. 47. The pharmaceutical composition of claim 46, wherein the consensus H3 hemagglutinin polypeptide is comprised in the composition of any one of claims 41 to 45. 48. The pharmaceutical composition of claim 46, wherein the consensus H3 hemagglutinin polypeptide comprises an amino acid sequence comprising SEQ ID NO: 3. 49. The pharmaceutical composition of claim 46, wherein the pharmaceutical composition is formulated as a vaccine. 50. A method for inducing an immune response in an animal against an influenza A virus (IAV), the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of claims 46 to 49. 51. The method of claim 50, wherein the immune response comprises a Cytotoxic T lymphocyte (CTL) response. 52. The method of claim 50, wherein the immune response comprises an IgG response. 85007-399822 -158- 53. The method of claim 50, wherein the immune response comprises a T cell response. 54. The method of claim 50, wherein the immune response comprises a T-helper/memory cell response. 55. The method of claim 50, wherein the immune response comprises an IFN-γ response. 56. The method of claim 50, wherein the administration is a prophylactic administration to the animal. 57. The method of claim 50, wherein the animal is a porcine. 58. The method of claim 50, wherein the method comprises a reduction in IAV viral load of the animal. 59. The method of claim 50, wherein the method comprises a reduction in IAV virus shedding by the animal. 60. A method of preventing an influenza A virus (IAV) infection in an animal, the method comprising the step of administering to the animal a therapeutically effective amount of the pharmaceutical composition of any one of claims 46 to 49. 61. The method of claim 60, wherein the administration is a prophylactic administration to the animal. 62. The method of claim 60,wherein the animal is a porcine. 63. The method of claim 60,wherein the method comprises a reduction in IAV viral load of the animal. 64. The method of claim 60,wherein the method comprises a reduction in IAV virus shedding by the animal.
EP23904695.6A 2022-12-16 2023-12-15 Swine influenza vaccine compositions and methods thereof Pending EP4633674A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263433242P 2022-12-16 2022-12-16
PCT/US2023/084345 WO2024130155A2 (en) 2022-12-16 2023-12-15 Swine influenza vaccine compositions and methods thereof

Publications (1)

Publication Number Publication Date
EP4633674A2 true EP4633674A2 (en) 2025-10-22

Family

ID=91486314

Family Applications (1)

Application Number Title Priority Date Filing Date
EP23904695.6A Pending EP4633674A2 (en) 2022-12-16 2023-12-15 Swine influenza vaccine compositions and methods thereof

Country Status (3)

Country Link
EP (1) EP4633674A2 (en)
CN (1) CN120731087A (en)
WO (1) WO2024130155A2 (en)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10279031B2 (en) * 2016-05-11 2019-05-07 Phibro Animal Health Corporation Composition comprising antigens and a mucosal adjuvant and a method for using
WO2020092207A1 (en) * 2018-10-28 2020-05-07 University Of Georgia Research Foundation Broadly reactive immunogens of influenza virus, compositions, and methods of use thereof

Also Published As

Publication number Publication date
CN120731087A (en) 2025-09-30
WO2024130155A2 (en) 2024-06-20
WO2024130155A3 (en) 2024-08-02

Similar Documents

Publication Publication Date Title
CN111088283B (en) mVSV viral vector, viral vector vaccine thereof and mVSV-mediated novel coronary pneumonia vaccine
TWI605124B (en) Novel baculovirus vectors and methods of ?use
WO2021160346A1 (en) Nucleic acid vaccine against the sars-cov-2 coronavirus
Wang et al. Recombinant adenovirus expressing F and H fusion proteins of peste des petits ruminants virus induces both humoral and cell-mediated immune responses in goats
Jiang et al. Hantavirus Gc induces long-term immune protection via LAMP-targeting DNA vaccine strategy
JP6951429B2 (en) New swine flu vaccine
CN102256997A (en) Torque teno virus (ttv) isolates and compositions
WO2021220246A1 (en) Recombinant sars-cov-2 polypeptides and uses
CN113444156B (en) Novel coronavirus pneumonia recombinant human adenovirus type 5 vaccine
CN101563361A (en) Influenza viruses capable of infecting canines and uses thereof
JP2023522154A (en) influenza vaccine
JP2013537409A (en) Parapox virus vector
CN109923125B (en) Immunogenic composition
CN103260644A (en) Parapoxvirus vector containing rabies virus antigen
CN104548087B (en) Epitope vaccine for resisting A/B subgroup avian leucosis virus infection and preparation method and application of epitope vaccine
Yang et al. Multivalent DNA vaccine enhanced protection efficacy against infectious bronchitis virus in chickens
AU2017317572B2 (en) New paramyxovirus and uses thereof
CN104306995B (en) Epitope vaccine for resisting subgroup J avian leukosis virus infection as well as preparation method and application of epitope vaccine
WO2024130155A2 (en) Swine influenza vaccine compositions and methods thereof
CN102847168B (en) The design of a kind of nucleic acid vaccine PV-Fn preventing bovine mastitis and structure thereof
US10881722B2 (en) Epizootic hemorrhagic disease vaccine
CN103865923A (en) Preparation and application of influenza virus-carried HAdV (human adenovirus) chimeric vaccine
Yuan et al. Antibody study in canine distemper virus nucleocapsid protein gene-immunized mice
CN113913393B (en) Recombinant Newcastle Disease Virus Vaccine for Novel Coronavirus Pneumonia
Kim et al. Preliminary study about sublingual administration of bacteria-expressed pandemic H1N1 influenza vaccine in miniature pigs

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20250710

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC ME MK MT NL NO PL PT RO RS SE SI SK SM TR

RAP3 Party data changed (applicant data changed or rights of an application transferred)

Owner name: CORNELL UNIVERSITY

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)