WO2022246084A1 - Sars-cov-2 polypeptides - Google Patents

Sars-cov-2 polypeptides Download PDF

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Publication number
WO2022246084A1
WO2022246084A1 PCT/US2022/030068 US2022030068W WO2022246084A1 WO 2022246084 A1 WO2022246084 A1 WO 2022246084A1 US 2022030068 W US2022030068 W US 2022030068W WO 2022246084 A1 WO2022246084 A1 WO 2022246084A1
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WIPO (PCT)
Prior art keywords
seq
amino acid
set forth
acid sequence
sequence set
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PCT/US2022/030068
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English (en)
French (fr)
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Gregory A. Poland
Inna G. Ovsyannikova
Richard B. Kennedy
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Mayo Foundation for Medical Education and Research
Mayo Clinic in Florida
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Mayo Foundation for Medical Education and Research
Mayo Clinic in Florida
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Priority to BR112023024034A priority Critical patent/BR112023024034A2/pt
Priority to EP22735677.1A priority patent/EP4294440A1/en
Priority to MX2023013665A priority patent/MX2023013665A/es
Priority to IL308465A priority patent/IL308465A/en
Priority to CA3212678A priority patent/CA3212678A1/en
Priority to JP2023571758A priority patent/JP2024521098A/ja
Priority to CN202280027143.4A priority patent/CN117479954A/zh
Priority to AU2022277697A priority patent/AU2022277697A1/en
Priority to KR1020237039921A priority patent/KR20240012394A/ko
Publication of WO2022246084A1 publication Critical patent/WO2022246084A1/en
Anticipated expiration legal-status Critical
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    • 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
    • A61K39/12—Viral antigens
    • A61K39/215—Coronaviridae, e.g. avian infectious bronchitis virus
    • 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
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5258—Virus-like particles
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
    • 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
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/20011—Coronaviridae
    • C12N2770/20022—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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/20011—Coronaviridae
    • C12N2770/20023—Virus like particles [VLP]
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/20011—Coronaviridae
    • C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/20011—Coronaviridae
    • C12N2770/20071—Demonstrated in vivo effect

Definitions

  • This document provides methods and materials related to selected severe acute respiratory distress coronavirus 2 (SARS-CoV-2) polypeptides.
  • SARS-CoV-2 selected severe acute respiratory distress coronavirus 2
  • this document provides vaccine compositions that contain one or more selected SARS-CoV-2 polypeptides provided herein and that have the ability to induce or increase immune responses against coronaviruses such as SARS-CoV-2 within a mammal (e.g., a human).
  • Peptide vaccines circumvent multiple issues inherent with live virus and inactivated vaccines - peptide vaccines are inexpensive, can be rapidly produced, require no cold chain, have extended (if not indefinite) stability, require no special training for use, and do not have contraindications prohibiting their use. Peptide vaccines can be safely administered to the young, the elderly, those with comorbidities, and the immunocompromised.
  • a selected SARS-CoV-2 polypeptide provided herein can be a substantially pure polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • This document also provides methods for increasing an immune response against a coronavirus infection (e.g., a SARS-CoV- 2 infection such as COVID-19) within a mammal (e.g., a human).
  • compositions that contain one or more selected SARS-CoV-2 polypeptides provided herein can be administered to a mammal (e.g., human) to induce or increase an immune response against a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) within the mammal.
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • compositions (e.g., vaccine compositions) that contain one or more selected SARS-CoV-2 polypeptides provided herein can be administered to a mammal (e.g., human) having or at risk of developing a coronavirus infection (e.g., a SARS- CoV-2 infection such as COVID-19) to treat the mammal.
  • selected SARS-CoV-2 polypeptides can induce broad recall immune responses against SARS-CoV-2.
  • the present disclosure provides selected SARS-CoV-2 polypeptides that can induce broad recall immune responses against SARS-CoV-2 polypeptides.
  • the present disclosure provides selected SARS-CoV-2 polypeptides that can induce broad recall immune responses against SARS-CoV-2 polypeptides from PBMCs of convalescent COVID-19 individuals. Having the ability to induce broad recall immune responses using selected SARS-CoV-2 polypeptides can enable the development of peptide- based vaccines that are inexpensive, can be rapidly produced, require little or no cold chain, have extended stability, and are not associated with contraindications.
  • one aspect of this disclosure provides substantially pure polypeptides consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs:l-87.
  • compositions comprising a substantially pure polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:5, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 37, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:40.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:21, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:46.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 44, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:45.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:3, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 16, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:28, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:31, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 17, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:24, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:43.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 8, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 10, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 11 , a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:43, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:53, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:38, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 34, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:72, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:78.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 78.
  • the composition can include one or more of an adjuvant or an immunostimulatory molecule.
  • the adjuvant or immunostimulatory molecule can be a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nanoparticles, or GLA.
  • RAG-I retinoic acid- in
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • the polypeptides disclosed herein are linked to poly(lactic-co-gly colic acid) (PLGA) nanoparticles.
  • the polypeptides are attached to one or more virus-like particles (VLP).
  • the VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • the VLPs are made from Q-beta bacteriophage
  • compositions including at least two polypeptides, where each of the at least two polypeptides is a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:5, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:40.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:21, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:46.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:44, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:45.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:3, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 16, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:28, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:31, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 17, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:24, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 43.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:8, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 10, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 11, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:43, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:53, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:38, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:34, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:72, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 78.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:78.
  • the composition can include an adjuvant or an immunostimulatory molecule.
  • the composition can include one or more
  • the adjuvant or immunostimulatory molecule can be a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04- like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles, or GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • CFA Complete Freund’s Ad
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04- like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • the polypeptides disclosed herein are linked to poly(lactic-co-glycolic acid) (PLGA) nanoparticles.
  • the polypeptides are attached to one or more virus-like particles (VLP).
  • the polypeptides are attached to one or more virus-like particles (VLP).
  • the VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • the VLPs are made from Q-beta bacteriophage.
  • this disclosure provides a composition comprising nucleic acids encoding a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:5, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 40.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:21, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:46.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:44, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:45.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:3, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 16, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:28, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:31, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 37.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 17, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:24, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:43.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 8, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 10, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 11 , a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:43, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:53, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:38, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 34, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:72, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:78.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 78.
  • the composition can include an adjuvant or an immunostimulatory molecule.
  • the composition can include one or more of an adjuvant or an immunostimulatory molecule.
  • the adjuvant or immunostimulatory molecule can be a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticle
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG- I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • the polypeptides disclosed herein are linked to poly(lactic-co-gly colic acid) (PLGA) nanoparticles.
  • the polypeptides are attached to one or more virus-like particles (VLP).
  • the polypeptides are attached to one or more virus-like particles (VLP).
  • the VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • the VLPs are made from Q-beta bacteriophage.
  • the nucleic acid can be in the form of a non-viral vector.
  • the non-viral vector can be an expression plasmid.
  • the nucleic acid can be in the form of a viral vector.
  • the viral vector can be a vector based on an adenoviruses, a vector based on an adeno-associated virus (AAV), a vector based on an retrovirus, a vector based on an lentivirus, a vector based on a measles virus, a vector based on a vesicular stomatitis virus, and a vector based on vaccinia virus.
  • AAV adeno-associated virus
  • this disclosure provides nucleic acid encoding at least two polypeptides, where each of the at least two polypeptides is a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:5, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:40.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:21, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:46.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:44, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:45.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:3, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 16, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:28, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:31, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 17, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:24, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 43.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 8, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 10, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 11, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:43, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:53, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:38, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:34, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:72, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 78.
  • the composition can include a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:78.
  • the composition can include an adjuvant or an immunostimulatory molecule.
  • the composition can include one or more of an adjuvant or an immunostimulatory molecule.
  • one or more adjuvants or immunostimulatory molecules can be a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nano
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • polypeptides disclosed herein are linked to poly(lactic-co-gly colic acid) (PLGA) nanoparticles.
  • polypeptides are attached to one or more virus-like particles (VLP).
  • the nucleic acid can be in the form of a non- viral vector.
  • the non-viral vector can be an expression plasmid.
  • the nucleic acid can be in the form of a viral vector.
  • the viral vector can be a vector based on an adenoviruses, a vector based on an adeno-associated virus (AAV), a vector based on an retrovirus, a vector based on an lentivirus, a vector based on a measles virus, a vector based on a vesicular stomatitis virus, and a vector based on vaccinia virus.
  • AAV adeno-associated virus
  • this disclosure provides methods for increasing an immune response against a coronavirus in a mammal.
  • the methods can comprise, or consist essentially of, administering to a mammal a composition including a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87 or nucleic acid encoding the polypeptide.
  • the mammal can be a human.
  • the coronavirus can be a SARS-CoV- 2.
  • the composition can include an adjuvant or an immunostimulatory molecule.
  • the composition can include one or more of an adjuvant or an immunostimulatory molecule.
  • one or more adjuvants or immunostimulatory molecules is selected from a group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles, and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4 toll-
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • the polypeptides disclosed herein are linked to poly(lactic-co-gly colic acid) (PLGA) nanoparticles.
  • the polypeptides are attached to one or more virus- like particles (VLP).
  • VLP virus-like particles
  • at least two doses of the composition are administered.
  • two doses of the composition are administered.
  • the polypeptide is presented on one or more virus-like particles (VLP).
  • the VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • the VLPs are made from Q-beta bacteriophage.
  • this disclosure provides methods for treating a mammal at risk of developing a coronavirus infection.
  • the methods can include, or consist essentially of, administering to a mammal at risk of developing a coronavirus infection a composition including a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87 or nucleic acid encoding the polypeptide.
  • the mammal can be a human.
  • the coronavirus infection can be COVID-19.
  • the composition can include an adjuvant or an immunostimulatory molecule.
  • the composition can include one or more of an adjuvant or an immunostimulatory molecule.
  • one or more adjuvants or immunostimulatory molecules can be a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles, and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • CFA Complete Freund’
  • adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4 toll-
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • the polypeptides disclosed herein are linked to poly(lactic-co-glycolic acid) (PLGA) nanoparticles.
  • the polypeptides are attached to one or more virus-like particles (VLP).
  • VLP virus-like particles
  • at least two doses of the composition are administered.
  • two doses of the composition are administered.
  • the polypeptide is presented on one or more virus-like particles (VLP).
  • the VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • the VLPs are made from Q-beta bacteriophage.
  • this document features methods for treating a mammal having a coronavirus infection.
  • the methods can include, or consist essentially of, administering to a mammal having a coronavirus infection a composition including a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87 or nucleic acid encoding the polypeptide.
  • the mammal can be a human.
  • the coronavirus infection can be COVID-19.
  • the composition can include an adjuvant or an immunostimulatory molecule.
  • the composition can include one or more of an adjuvant or an immunostimulatory molecule.
  • one or more adjuvants or immunostimulatory molecules can be a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nanoparticles, and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • CFA Complete Freund’
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • the polypeptides disclosed herein are linked to poly(lactic-co-gly colic acid) (PLGA) nanoparticles.
  • the polypeptides are attached to one or more virus-like particles (VLP).
  • VLP virus-like particles
  • at least two doses of the composition are administered.
  • two doses of the composition are administered.
  • the polypeptide is presented on one or more virus-like particles (VLP).
  • the VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • the VLPs are made from Q-beta bacteriophage.
  • FIGS. 1A and B IFN-g ELISPOT responses to SARS-CoV-2 polypeptides pool stimulation.
  • FIGS. 2A, 2B, and 2C IFN-g ELISPOT responses to individual SARS-CoV-2 polypeptides.
  • FIG. 3 Peptides induced immune responses in an animal hamster model.
  • FIG. 4 Immune responses induced by peptides formulated with different adjuvants in hamsters.
  • FIGS. 5A, 5B, 5C, 5D, and 5E Immune responses induced by different peptides in hamsters as measured by IgG ELISA.
  • FIGS. 6A, 6B, 6C, 6D, and 6E Immune responses induced by different peptides in hamsters as measured by IFN-g ELISPOT.
  • FIG. 7 Summary of immune responses induced by different peptides in hamsters.
  • FIGS. 8A, 8B, 8C, 8D, 8E, 8F, 8G, and 8H Immune responses in hamsters induced by five peptides in combination with different adjuvants, as measured by IgG ELISA.
  • FIGS. 9A, 9B, 9C, 9D, 9E, 9F, 9G, and 9H Immune responses in hamsters induced by five peptides in combination with different adjuvants, as measured by IFN-g ELISPOT.
  • FIGS. 10A, 10B, IOC, 10D, 10E, 10F, 10G, 10H, and 101 Immune responses in mice induced by combinations of peptides, formulated with CFA/IFA + CpG, as measured by IgG ELISA.
  • FIGS. 11 A, 11B, 11C, 11D, 11E, 11F, 11G, 11H, 111 Immune responses in mice induced by combinations of peptides, formulated with CFA/IFA + CpG, as measured by IFN-g ELISPOT.
  • FIG. 12 Summary of immune responses induced by different peptides in mice.
  • FIGS. 13A, 13B, 13C, 13D, 13E, 13F, 13G, and 13H Immune responses in mice induced by different peptides, given in two doses at 21 -day or 28-day intervals, as measured by ELISA (FIGS. 13 A, 13B, 13C, and 13D) and IFN-g ELISPOT (FIGS. 13E, 13F, 13G, and 13H).
  • FIGS. 14A, 14B, 14C, 14D, 14E, 14F, 14G, and 14H Immune responses in mice induced by 10 peptides, formulated with different adjuvants, as measured by IgG ELISA (FIGS. 14 A, 14B, 14C, and 14D) and IFN-g ELISPOT (FIGS. 14E, 14F, 14G, and 14H).
  • FIGS. 15 A, 15B, 15C, 15D, 15E, 15F, 15G, 15H, 151, 15J, 15K, and 15L Immune responses in mice induced by different long peptides, as measured by IgG ELISA.
  • FIGS. 16 A, 16B, 16C, 16D, 16E, 16F, 16G, 16H, 161, 16J, 16K, and 16L Immune responses in mice induced by different long peptides, as measured by IFN-g ELISPOT.
  • FIGS. 17A and 17B Immune responses in mice induced by different long peptides, as measured by IgG ELISA.
  • FIGS. 18 A, 18B, 18C, 18D, 18E, 18F, 18G, 18H, 181, 18J, 18K, and 18L Summary of immune responses in mice induced by different long peptides, as measured by IgG ELISA, and performed at different serial dilutions.
  • FIG. 19 Immune responses in mice induced by different long peptides, as measured by a neutralizing antibody assay (pseudovirus microneutralization assay).
  • FIGS. 20 A, 20B, 20C, and 20D Immune responses in mice induced by different long peptides presented on virus-like particles (VLPs), as measured by IgG ELISA (FIGS. 20A and 20C) and IFN-g ELISPOT (FIGS. 20B and 20D).
  • VLPs virus-like particles
  • FIGS. 21A, 21B, 21C, and 21D Immune responses in mice induced by different long peptides presented on virus-like particles (VLPs), as measured by IgG ELISA (FIGS. 21A and 21C) and IFN-g ELISPOT (FIGS. 21B and 21D).
  • VLPs virus-like particles
  • FIGS. 22A, 22B, 22C, and 22D Immune responses in mice induced by different long peptides presented on virus-like particles (VLPs), as measured by IgG ELISA (FIGS. 22A and 22C) and IFN-g ELISPOT (FIGS. 22B and 22D).
  • FIGS. 23 A, 23B, 23C, and 23D Immune responses in mice induced by different long peptides presented on virus-like particles (VLPs), as measured by IgG ELISA (FIGS. 23A and 23C) and IFN-g ELISPOT (FIGS. 23B and 23D).
  • FIGS. 24A, 24B, 24C, and 24D Immune responses in mice induced by different long peptides presented on virus-like particles (VLPs), as measured by IgG ELISA (FIGS. 24A and 24C) and IFN-g ELISPOT (FIGS. 24B and 24D).
  • VLPs virus-like particles
  • FIGS. 25 A, 25B, 25C, and 25D Immune responses in mice induced by different long peptides presented on virus-like particles (VLPs), as measured by IgG ELISA (FIGS. 25A and 25C) and IFN-g ELISPOT (FIGS. 25B and 25D).
  • VLPs virus-like particles
  • FIGS. 26A, 26B, 26C, and 26D Immune responses in mice induced by different long peptides presented on virus-like particles (VLPs) and empty VLPs, as measured by IgG ELISA (FIGS. 26 A and 26B) and IFN-g ELISPOT (FIGS. 26C and 26D).
  • FIGS. 27 A, 27B, 27C, 27D, 27E, 27F, 27G, and 27H Immune responses in mice induced by different peptides with and without the RBD protein, as measured by IgG ELISA (FIGS.
  • FIGS. 28A, 28B, 28C, and 28D Peptide-specific antibody titers (as measured by ELISA shown in the left panel) and peptide-specific T cell responses (as measured by ELISPOT as shown in the right panel) induced by Pfizer mRNA vaccine in hamsters.
  • FIGS. 28A, 28B, 28C, and 28D Peptide-specific antibody titers (as measured by ELISA shown in the left panel) and peptide-specific T cell responses (as measured by ELISPOT as shown in the right panel) induced by Pfizer mRNA vaccine in hamsters.
  • 29 A, 29B, 29C, and 29D Peptide-specific antibody titers (as measured by ELISA shown in the left panel) and peptide-specific T cell responses (as measured by ELISPOT as shown in the right panel) induced by Pfizer mRNA vaccine in mice.
  • FIGS. 30A, 30B, 30C, and 30D Peptide-specific antibody titers (as measured by ELISA shown in the left panel) and peptide-specific T cell responses (as measured by ELISPOT as shown in the right panel) induced by 6 selected long peptides in hamsters.
  • the methods disclosed herein include and comprise one or more steps or actions for achieving the described method.
  • the method steps and/or actions may be interchanged with one another without departing from the scope of the present disclosure.
  • the order and/or use of specific steps and/or actions may be modified without departing from the scope of the present disclosure.
  • phrases such as “between X and Y” and “between about X and Y” should be interpreted to include X and Y.
  • phrases such as “between about X and Y” mean “between about X and about Y” and phrases such as “from about X to Y” mean “from about X to about Y.”
  • exemplary is used to mean serving as an example, instance, or illustration. Any aspect or aspect described as “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or aspects, nor is it meant to preclude equivalent structures and techniques known to those of ordinary skill in the art. Rather, use of the word exemplary is intended to present concepts in a concrete fashion, and the disclosed subject matter is not limited by such examples.
  • a selected SARS-CoV-2 polypeptide provided herein can be a substantially pure polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • the term “substantially pure” as used herein with reference to a polypeptide means the polypeptide is substantially free of other polypeptides, lipids, carbohydrates, and nucleic acid with which it is naturally associated.
  • a substantially pure polypeptide is any polypeptide that is removed from its natural environment and is at least 60 percent pure.
  • a substantially pure polypeptide can be at least about 65, 70, 75, 80, 85, 90, 95, or 99 percent pure. Typically, a substantially pure polypeptide will yield a single major band on a non-reducing polyacrylamide gel. In some cases, a substantially pure polypeptide provided herein can be a polypeptide that is synthesized to have a purity of at least about 60, 65, 70, 75, 80, 85, 90, 95, or 99 percent.
  • a SARS-CoV-2 polypeptide provided herein can have HLA class I binding properties.
  • a SARS-CoV-2 polypeptide provided herein can have HLA class II binding properties.
  • a SARS-CoV-2 polypeptide provided herein can be any appropriate length (e.g., can include any number of amino acids).
  • a SARS-CoV-2 polypeptide provided herein can be from about 7 amino acids in length to about 100 amino acids (e.g., from about 7 to about 80 amino acids, from about 7 to about 60 amino acids, from about 7 to about 50 amino acids, from about 7 to about 40 amino acids, from about 7 to about 30 amino acids, from about 7 to about 20 amino acids, from about 7 to about 15 amino acids, from about 10 to about 100 amino acids, from about 20 to about 100 amino acids, from about 30 to about 100 amino acids, from about 40 to about 100 amino acids, from about 50 to about 100 amino acids, from about 60 to about 100 amino acids, from about 70 to about 100 amino acids, from about 80 to about 100 amino acids, from about 10 to about 80 amino acids, from about 20 to about 70 amino acids, from about 30 to about 60 amino acids, from about 40 to about 50 amino acids, from about 10 to about 20 amino acids, from about 30 to about 60
  • a SARS-CoV-2 provided herein can be from about 8 to about 12 amino acid sequences in length.
  • a SARS-CoV-2 polypeptide provided herein and having HLA class I binding properties can be from about 8 to about 12 amino acid sequences in length.
  • a SARS-CoV-2 polypeptide provided herein can be from about 13 to about 25 amino acid sequences in length.
  • a SARS-CoV-2 polypeptide provided herein and having HLA class II binding properties can be from about 13 to about 25 amino acid sequences in length.
  • a SARS-CoV-2 polypeptide provided herein can be from about 35 to about 45 amino acid sequences in length.
  • a SARS-CoV-2 polypeptide provided herein can be from about 38 to about 42 amino acid sequences in length. In an aspect, a SARS-CoV-2 polypeptide provided herein can be from about 39 to about 41 amino acid sequences in length. In an aspect, a SARS-CoV-2 polypeptide provided herein can be about 40 amino acid sequences in length.
  • long peptide refers to a peptide longer than 30 amino acids, but shorter than 50 amino acids.
  • long peptides allow for beter display of 3-dimensional structures, and can include multiple smaller epitopes (both B cell and T cell epitopes) within the longer peptide sequence.
  • a long peptide provided herein can be from about 35 to about 45 amino acid sequences in length.
  • a long peptide provided herein can be from about 38 to about 42 amino acid sequences in length.
  • a long peptide provided herein can be from about 39 to about 41 amino acid sequences in length.
  • a long peptide provided herein can be about 40 amino acid sequences in length.
  • a SARS-CoV-2 polypeptide provided herein can be derived from any SARS-CoV-2 polypeptide.
  • polypeptide vaccines derived from spike (S) protein only may allow for the development of further viral mutants that can escape, in part or in whole, antibody -mediated immunity.
  • a SARS-CoV-2 polypeptide provided herein can be derived from a structural SARS-CoV-2 polypeptide (e.g., a SARS-CoV-2 spike (S)-protein such as a receptor-binding domain (RBD) of a SARS-CoV-2 S-protein, a SARS- CoV-2 nucleocapsid (N)-protein, and a SARS-CoV-2 membrane (M)-protein).
  • S SARS-CoV-2 spike
  • RBD receptor-binding domain
  • N SARS-CoV-2 nucleocapsid
  • M SARS-CoV-2 membrane
  • a SARS-CoV-2 polypeptide provided herein can be derived from anon-structural SARS-CoV-2 polypeptide (e.g., a polypeptide encoded by ORFlab, a polypeptide encoded by ORF3a, and a polypeptide encoded by ORF9b).
  • a SARS-CoV-2 polypeptide provided herein can comprise, consist essentially of, or consist of the amino acid sequence set forth in Table 1.
  • a SARS-CoV-2 polypeptide provided herein that consists essentially of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87 is a polypeptide that has zero, one, two, or three amino acid substitutions within the articulated sequence of the sequence identifier (e.g., SEQ ID NO: 1), has zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., SEQ ID NO:l), and/or has zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., SEQ ID NO:l), provided that the SARS-CoV-2 polypeptide has the ability to induce or increase immune responses against a coronavirus such as SARS-CoV-2 within a mammal (e.g., a human).
  • SARS-CoV-2 polypeptides that consist essentially of the amino acid sequence set forth in any one of SEQ ID NOs: 1
  • a SARS-CoV-2 polypeptide provided herein comprises the amino acid sequence set forth in any one of SEQ ID NOs:l-87 and 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acid residues preceding the sequence (e.g., SEQ ID NO: 1), wherein the preceding sequence is from a naturally-found SARS-CoV-2 peptide sequence, provided that the SARS-CoV-2 polypeptide has the ability to induce or increase immune responses against a coronavirus such as SARS-CoV-2 within a mammal (e.g., a human).
  • a mammal e.g., a human
  • a SARS-CoV-2 polypeptide provided herein comprises the amino acid sequence set forth in any one of SEQ ID NOs:l-87 and 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acid residues following the sequence (e.g., SEQ ID NO: 1), wherein the succeeding sequence is from a naturally-found SARS-CoV-2 peptide sequence, provided that the SARS-CoV-2 polypeptide has the ability to induce or increase immune responses against a coronavirus such as SARS-CoV-2 within a mammal (e.g., a human).
  • a SARS-CoV-2 polypeptide provided herein comprises the amino acid sequence set forth in any one of SEQ ID NOs: 1-87 is flanked on both ends by 0, 1, 2, 3, 4, 5, 6,
  • SARS-CoV-2 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acid residues from a naturally-found SARS-CoV-2 peptide sequence, wherein the preceding and succeeding amino acid sequences may be of different lengths, provided that the SARS-CoV-2 polypeptide has the ability to induce or increase immune responses against a coronavirus such as SARS-CoV-2 within a mammal (e.g., a human).
  • Class I and class II molecules are important for T cell-mediated adaptive immunity. Without being bound by theory, HLA Class I molecules recognize antigenic peptides of approximately 8-10 amino acids in length, while HLA Class II molecules recognize antigenic peptides of approximately 12-24 amino acids in length.
  • the peptides of the present disclosure are based, in part, on the surprising result that longer peptides of about 40 amino acids are equally or more immunogenic than shorter peptides up to 28 amino acids in length.
  • a SARS-CoV-2 polypeptide provided herein comprises, consists essentially of, or consists of the amino acid sequence set forth in Table 3. Sequences listed in bold correspond to the short peptide or peptides contained within the longer sequence. Table 3. Exemplary SARS-CoV-2 polypeptides.
  • a SARS-CoV-2 polypeptide provided herein e.g., a substantially pure polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87
  • a coronavirus such as SARS-CoV-2 within a mammal (e.g., a human).
  • a SARS-CoV-2 polypeptide provided herein e.g., a substantially pure polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87
  • nucleic acid encoding a SARS-CoV-2 polypeptide provided herein e.g., nucleic acid encoding a polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87
  • a mammal e.g., a human
  • an immune response e.g., an antibody response and/or a T cell response
  • Any appropriate method can be used to identify the presence of an immune response against a coronavirus such as SARS-CoV-2.
  • SARS-CoV-2 polypeptide provided herein (e.g., a substantially pure polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87).
  • a SARS- CoV-2 polypeptide provided herein e.g., a substantially pure polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87
  • SARS-CoV-2 polypeptide e.g., a substantially pure polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87
  • SARS-CoV-2 polypeptide e.g., cells engineered to express the SARS-CoV-2 polypeptide of interest from exogenous nucleic acid encoding that SARS-CoV-2 polypeptide or cells infected with a virus (e.g., SARS-CoV-2) that express the SARS-CoV-2 polypeptide of interest from that virus) or by synthesizing the SARS-CoV-2 polypeptide of interest using appropriate polypeptide synthesizing techniques (e.g., solution phases synthesis (SPS), solid phase peptid
  • one or more SARS-CoV-2 polypeptides provided herein can be presented on a particle.
  • one or more SARS-CoV-2 polypeptides provided herein e.g., one or more polypeptides that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87
  • one or more SARS-CoV-2 polypeptides provided herein are presented on a virus-like particle (VLP).
  • VLPs are nanostructures that closely resemble viruses, with diverse applications in immunization, therapeutics, and diagnostics. VLPs possess self-adjuv anting properties and allow for highly repetitive presentation of over 170 epitopes on its surface. In addition to enhanced antigen presentation, packaging peptides with VLPs may reduce the amount of peptide needed per dose to about 5%-10% of the dose of unpackaged peptides.
  • VLPs are also easier to administer via various routes of administration than emulsions.
  • one or more SARS-CoV-2 polypeptides provided herein e.g., one or more polypeptides that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87
  • VLP virus-like particle
  • Parvoviridae e.g. adeno-associated virus
  • Retroviridae e.g. HIV
  • Flaviviridae e.g. Hepatitis C virus
  • Paramyxoviridae e.g. Nipah
  • bacteriophages e.g. z
  • one or more SARS-CoV-2 polypeptides provided herein are presented on a virus-like particle (VLP) made from bacteriophage Q .
  • VLP virus-like particle
  • one or more SARS-CoV-2 polypeptides provided herein are presented on a poly(lactic-co-gly colic acid) (PLGA) nanoparticle.
  • the VLP -peptide or PLGA-peptide is formulated with one or more adjuvants and one or more immunostimulatory agents.
  • adjuvants and one or more immunostimulatory molecules that can be formulated with the VLP -peptide or PLGA-peptide include, without limitation, CpG oligonucleotide motifs, aluminum (e.g., aluminum salts such as aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, and microfluidized aluminum salts), monophosphoryl lipid A, aluminumphosphylate, MF59, MF59-like, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, and GLA.
  • aluminum salts such as aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, and microfluidized aluminum salts
  • monophosphoryl lipid A aluminumphosphylate
  • one or more adjuvants or immunostimulatory molecules can be a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles, and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • CFA Complete Freund’
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • the polypeptides disclosed herein are linked to poly(lactic-co-glycolic acid) (PLGA) nanoparticles.
  • the polypeptides are attached to one or more virus-like particles (VLP).
  • VLP virus-like particles
  • the VLP-peptide is formulated with Alum and CpG.
  • the VLP-peptide is formulated with Montanide 51 and CpG or GLA.
  • This document also provides nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more polypeptides that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87).
  • this document provides vectors (e.g., plasmids and viral vectors) that include nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more polypeptides that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87) in a manner such that the SARS-CoV-2 polypeptide can be expressed within a cell.
  • a vector including nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein is a non- viral vector
  • any appropriate non-viral vector can be used.
  • a non-viral vector can be an expression plasmid (e.g., a cDNA expression vector).
  • a vector including nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein is a viral vector
  • any appropriate viral vector can be used.
  • a viral vector can be derived from a positive-strand virus or a negative-strand virus.
  • a viral vector can be derived from a virus having a single- stranded genome or a virus having a double stranded genome.
  • a viral vector can be derived from a virus with a DNA genome or a RNA genome. In some cases, a viral vector can be a chimeric viral vector.
  • a viral vector can infect dividing cells. In some cases, a viral vector can infect non-dividing cells.
  • virus-based vectors that can including nucleic acid encoding a SARS-CoV-2 polypeptide provided herein (e.g., a polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs:l-87) include, without limitation, virus-based vectors based on adenoviruses, adeno-associated viruses (AAVs), retroviruses, lentiviruses, measles viruses, vesicular stomatitis viruses, and vaccinia viruses.
  • AAVs adeno-associated viruses
  • a vector e.g., a plasmid or a viral vector
  • a vector can contain one or more regulatory elements operably linked to the nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein.
  • regulatory elements can include promoter sequences, enhancer sequences, response elements, signal peptides, internal ribosome entry sequences, polyadenylation signals, terminators, and inducible elements that modulate expression (e.g., transcription or translation) of a nucleic acid.
  • the choice of regulatory element(s) that can be included in a vector depends on several factors, including, without limitation, inducibility, targeting, and the level of expression desired.
  • a promoter can be included in a vector to facilitate transcription of a nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein (e.g., a polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87).
  • a promoter can be a naturally occurring promoter or a recombinant promoter.
  • a promoter can be constitutive or inducible (e.g., in the presence of tetracycline), and can affect the expression of a nucleic acid encoding a polypeptide in a general or cell/tissue-specific manner.
  • promoters that can be used to drive expression of one or more SARS-CoV-2 polypeptides provided herein (e.g., a polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87) in cells include, without limitation, CMV promoters, EF la promoters, SV40 promoters, PGK1 promoters, Ubc promoters, TRE promoters, and CAG promoters.
  • “operably linked” refers to positioning of a regulatory element in a vector relative to a nucleic acid encoding a polypeptide in such a way as to permit or facilitate expression of the encoded polypeptide.
  • a vector can contain a promoter and nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein.
  • the promoter is operably linked to a nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein such that it drives expression of the SARS- CoV-2 polypeptide(s) in cells.
  • compositions that include one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) of the SARS-CoV-2 polypeptides provided herein and/or nucleic acid encoding one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) of the SARS-CoV-2 polypeptides provided herein.
  • a composition provided herein can include one or more of the SARS-CoV-2 polypeptides set forth in Table 1 (or nucleic acid encoding those SARS-CoV-2 polypeptides).
  • composition provided herein can include one or more of the SARS-CoV-2 polypeptides set forth in Table 2 (or nucleic acid encoding those SARS-CoV-2 polypeptides).
  • a composition provided herein can include one or more of the SARS-CoV-2 polypeptides set forth in Table 3 (or nucleic acid encoding those SARS-CoV-2 polypeptides).
  • a composition provided herein can include at least two (e.g., two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) of the SARS-CoV-2 polypeptides provided herein and/or nucleic acid encoding at least two (e.g., two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) of the SARS-CoV-2 polypeptides provided herein.
  • a composition provided herein can include at least two of the SARS-CoV-2 polypeptides set forth in Table 1 (or nucleic acid encoding those SARS-CoV-2 polypeptides).
  • a composition provided herein can include at least two of the SARS-CoV-2 polypeptides set forth in Table 2 (or nucleic acid encoding those SARS-CoV-2 polypeptides).
  • a composition provided herein can include at least two of the SARS-CoV-2 polypeptides set forth in Table 3 (or nucleic acid encoding those SARS-CoV-2 polypeptides).
  • a composition provided herein can include at least two of the SARS-CoV-2 polypeptides set forth in Tables 1, 2, and 3. Examples of other specific combinations of polypeptides that can be used to make a composition provided herein include, without limitation, those set forth in Table 4.
  • compositions provided herein e.g., a composition that includes one or more of the SARS-CoV-2 polypeptides provided herein and/or nucleic acid encoding one or more of the SARS-CoV-2 polypeptides provided.
  • the one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding such one or more SARS-CoV-2 polypeptides) can be combined with a pharmaceutically acceptable carrier and/or a pharmaceutical excipient.
  • pharmaceutically acceptable refers to generally non-toxic, inert, and/or physiologically compatible compounds.
  • pharmaceutical excipient includes materials such as carriers, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, colorants, and preservatives.
  • a composition provided herein can be a vaccine composition.
  • a composition containing one or more polypeptides set forth in SEQ ID NOs:l-87 can be formulated into a polypeptide-based vaccine for use in a mammal (e.g., a human). Any appropriate method can be used to formulate a polypeptide-based vaccine such as those described elsewhere (Belyakov et al., Proc. Natl. Acad. Sci.
  • a vaccine composition provided herein can include one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87) and/or nucleic acid encoding one or more of the SARS-CoV-2 polypeptides provided herein (e.g., nucleic acid encoding one or more SARS- CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87) in combination with one or more adjuvants and/or one or more immunostimulatory molecules.
  • SARS-CoV-2 polypeptides provided herein e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87
  • adjuvants and one or more immunostimulatory molecules that can be included within a vaccine composition provided herein include, without limitation, CpG oligonucleotide motifs, aluminum (e.g., aluminum salts such as aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, and microfluidized aluminum salts), monophosphoryl lipid A, aluminumphosphylate, MF59, MF59-like, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, and GLA.
  • CpG oligonucleotide motifs e.g., aluminum salts such as aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, and microfluidized aluminum salts
  • monophosphoryl lipid A aluminumphosphylate
  • MF59, MF59-like AS03, AS04, AS03-like, AS04-like, ASOlB-like
  • one or more adjuvants or immunostimulatory molecules can be formulated with the vaccine compositions provided herein include, but are not limited to, a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IFA), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IFA), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • CFA Complete Freund’s Adjuvant
  • IFA Incomplete Freund’s
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • TLR4
  • one or more adjuvants or immunostimulatory molecules is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • an adjuvant or immunostimulatory molecule included within a vaccine composition provided herein can be a non-naturally occurring (e.g., artificial) adjuvant or immunostimulatory molecule.
  • a vaccine composition provided herein can include one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1- 87) and/or nucleic acid encoding one or more of the SARS-CoV-2 polypeptides provided herein (e.g., nucleic acid encoding one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87), one or more adjuvants and/or one or more immunostimulatory molecules, and one or more pharmaceutically acceptable carriers and/or pharmaceutical excipients.
  • a vaccine composition provided herein can be a multivalent vaccine composition having the ability to induce or increase immune responses against multiple members of the coronavirus family within a mammal (e.g., a human).
  • a vaccine composition provided herein can have the ability to induce or increase immune responses against SARS-CoV-2, 229E, NL63, OC43, HKU1, Middle East Respiratory Syndrome (MERS)- CoV, Severe Acute Respiratory Syndrome (SARS)-CoV, or any combination thereof.
  • a vaccine composition provided herein can be used as a multivalent vaccine composition having the ability to induce or increase immune responses against one or more lineages, clades, variants, or strains of SARS-CoV-2.
  • a vaccine composition provided herein can have the ability to induce or increase immune responses against B.l.1.7, B.1.351, P.1, P.2,
  • a vaccine composition provided by the present disclosure may induce or increase immune responses against future-identified coronavirus variants, or mutants or recombinants of existing variants.
  • This document also provides methods for increasing an immune response against a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) within a mammal (e.g., a human).
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • a mammal e.g., a human
  • one or more SARS-CoV-2 polypeptides provided herein e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87
  • nucleic acid encoding one or more of the SARS-CoV-2 polypeptides provided herein e.g., nucleic acid encoding one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87
  • one or more SARS-CoV-2 polypeptides provided herein can be administered to a mammal (e.g., a human) having or at risk of developing a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) to treat that mammal.
  • a mammal e.g., a human
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • the terms “treat” or “treatment” is an approach for obtaining beneficial or desired clinical results.
  • the terms “treat” or “treatment” means to administer a SARS-CoV-2 polypeptide disclosed herein that partially or completely alleviates, ameliorates, relieves, inhibits, delays onset of, reduces severity of, and/or reduces incidence of one or more symptoms, features and causes of a SARS-CoV-2 infection (e.g., a COVID-19 infection).
  • treat or “treatment” includes the administration of a SARS-CoV-2 polypeptide disclosed herein to prevent or delay the onset of a symptom, complication, or biochemical indicia of a SARS-CoV-2 infection, alleviating a symptom or arresting or inhibiting further development of a SARS-CoV-2 infection.
  • Treatment may be prophylactic (to prevent or delay the onset of the SARS-CoV-2 infection, or to prevent the manifestation of a clinical or subclinical symptom thereof) or therapeutic suppression or alleviation of a symptom after the manifestation of the SARS-CoV-2 infection.
  • Any appropriate mammal can be administered one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87) and/or nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein (e.g., nucleic acid encoding one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87) to treat that mammal.
  • SARS-CoV-2 polypeptides provided herein e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87
  • nucleic acid encoding one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist
  • Examples of mammals that can be administered one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARSCoV-2 polypeptides provided herein) include, without limitation, humans, non-human primates (e.g., monkeys or apes), horses, dogs, cats, bovine species, pigs, sheep, mice, rats, hamsters, bats, foxes, goats, mink, and deer.
  • a human identified as having or as being at risk of developing a coronavirus infection can be administered one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein) to treat that human.
  • a human identified as having or as being at risk of developing a severe illness from a coronavirus infection can be administered one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARS- CoV-2 polypeptides provided herein) to treat that human.
  • a human identified as immunocompromised can be administered one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein) to treat that human.
  • a human identified as an organ transplant recipient can be administered one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein) to treat that human.
  • a human who is diabetic can be administered one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein) to treat that human.
  • the methods described herein can include identifying a mammal (e.g., a human) as needing an induction or an increase in an immune response against a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19).
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • humans identified as having been in recent (e.g., within one to two weeks) contact with one or more humans having or suspected of having a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID- 19
  • humans who have tested positive for SARS-CoV-2 infection by a polymerase chain reaction (PCR) or rapid antigen test is identified as needing an induction or an increase in an immune response against a coronavirus such as SARS-CoV-2 and can be administered a vaccine composition provided herein.
  • PCR polymerase chain reaction
  • one or more SARS-CoV-2 polypeptides provided herein can be used to induce or increase an immune response against a coronavirus such as SARS-CoV-2 within a mammal (e.g., a human).
  • a coronavirus such as SARS-CoV-2 within a mammal (e.g., a human).
  • a vaccine composition provided herein can be administered to a mammal (e.g., a human) in need thereof (e.g., a mammal needing an induction or an increase in an immune response against a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) such as a mammal having or at risk of developing COVID-19) to induce or increase an immune response (e.g., an antibody response and/or aT cell response) against a coronavirus such as SARS-CoV-2.
  • an immune response against a coronavirus such as SARS-CoV-2 within a mammal e.g., a human
  • an immune response against a coronavirus such as SARS-CoV-2 within a mammal can be a cellular immune response.
  • the immune response can be a T helper type 1 (TH1) cell-mediated response, a TH2 cell-mediated response, or a combination thereof.
  • TH1 T helper type 1
  • the immune response can involve any appropriate T cells (e.g., CD4 + T cells and CD8 + T cells).
  • an induction or an increase (or decrease) of immune response against a coronavirus is measured by immune assays.
  • an increase of immune response is measured by quantification of IFN-g by enzyme- linked immunosorbent assays (ELISAs).
  • ELISAs enzyme- linked immunosorbent assays
  • Exemplary ELISA kits are commercial available at vendors, e.g., Immulon 4 HBX from Thermo Fisher Scientific, and can be performed in accordance with the manufacturer’s instructions.
  • an increase of immune response is measured by quantification of cytokine production (e.g., IFN-g) by ELISPOT assays.
  • ELISPOT kits are commercially available at vendors, e.g., BD Biosciences (BD ELISPOT assay), and can be performed in accordance with the manufacturer’s instructions.
  • an increase of immune response is measured by quantification of IgG.
  • an increase of immune response is measured by quantification of IgM.
  • an increase of immune response is measured by quantification of total binding antibody or neutralizing antibody (measured by microneutralization assays or plaque-reduction assays).
  • an increase of immune response is measured by a chemiluminescence immunoassay (CLIA).
  • an increase of immune response is measured by an enzyme-linked immunosorbent assays (ELISA).
  • an increase of immune response is measured by an electrochemiluminescence immunoassay (ECLIA).
  • an increase of immune response is measured by a fluorescent microsphere Immunoassay (FMIA).
  • an increase of immune response is measured by a chemiluminescent microparticle immunoassay (CMIA).
  • an increase of immune response is measured by an enzyme-linked fluorescence assay (ELF A).
  • an increase in immune response is quantified relative to known negative and positive controls. Some assays are quantified relative to calibrated standards (e.g., WHO International Standard - a pooled reference serum with a defined quantity of SARS-CoV-2 antibody and a defined neutralizing activity against SARS-CoV-2).
  • one or more SARS-CoV-2 polypeptides provided herein can be used to delay or prevent the development of one or more symptoms of a coronavirus infection (e.g., a SARS- CoV-2 infection such as COVID-19) within a mammal at risk of developing a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19).
  • a coronavirus infection e.g., a SARS- CoV-2 infection such as COVID-19
  • a coronavirus infection e.g., a SARS- CoV-2 infection such as COVID-19
  • one or more SARS- CoV-2 polypeptides provided herein can be administered to a mammal (e.g., a human) in need thereof (e.g., a mammal needing an induction or an increase in an immune response against a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) such as a mammal having or at risk of developing COVID-19) to delay or prevent the development of one or more symptoms of a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) in the mammal.
  • a mammal e.g., a human
  • a mammal needing an induction or an increase in an immune response against a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) such as a mammal having or at risk of developing COVID-19)
  • a coronavirus infection e.g.,
  • Symptoms of a coronavirus infection include, without limitation, fever, chills, cough, shortness of breath, difficulty breathing, fatigue, muscle aches, body aches, headache, loss of taste, loss of smell, sore throat, congestion, runny nose, nausea, vomiting, diarrhea, persistent pain or pressure in the chest, arterial thromboses, venous thromboses, and ventilatory failure.
  • the materials and methods described herein can be used to delay the onset of one or more symptoms of a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) within a mammal at risk of developing a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent.
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • one or more SARS-CoV-2 polypeptides provided herein can be used to reduce the duration and/or the severity of one or more symptoms of a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) present within a mammal having a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19).
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • one or more SARS- CoV-2 polypeptides provided herein can be administered to a mammal (e.g., a human) in need thereof (e.g., a mammal needing an induction or an increase in an immune response against a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) such as a mammal having or at risk of developing COVID-19) to reduce the duration and/or the severity of one or more symptoms of a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) within the mammal.
  • a mammal e.g., a human
  • a mammal needing an induction or an increase in an immune response against a coronavirus infection
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • a coronavirus infection e.g., a SARS-CoV
  • Symptoms of a coronavirus infection include, without limitation, fever, chills, cough, shortness of breath, difficulty breathing, fatigue, muscle aches, body aches, headache, loss of taste, loss of smell, sore throat, congestion, runny nose, nausea, vomiting, diarrhea, persistent pain or pressure in the chest, arterial thromboses, venous thromboses, and ventilatory failure.
  • the methods and materials described herein can be used to reduce the duration and/or the severity of one or more symptoms of one or more symptoms of a coronavirus infection (e.g., a SARS-CoV-2 infection such as COVID-19) present within a mammal having a coronavirus infection (e.g., a SARS- CoV-2 infection such as COVID-19) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent.
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • a coronavirus infection e.g., a SARS-CoV-2 infection such as COVID-19
  • a composition e.g., a vaccine composition
  • a mammal e.g., a human
  • intramuscularly e.g., via intramuscular injection
  • subcutaneously e.g., via a subcutaneous injection
  • intranasally transcutaneously, or via inhalation.
  • the route and/or mode of administration of a composition e.g., a vaccine composition
  • a composition e.g., a vaccine composition
  • different doses of a composition are administered to a mammal by the same route of administration.
  • different doses of a composition e.g., a vaccine composition
  • a first dose of one or more SARS-CoV-2 polypeptides provided herein e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87
  • an effective amount of one or more SARS-CoV-2 polypeptides provided herein can be an amount that induces or increases an immune response against a coronavirus such as SARS-CoV-2 within the mammal (e.g., a human) without producing significant toxicity to the mammal.
  • the effective amount can remain constant or can be adjusted as a sliding scale or variable dose depending on the mammal’s response to treatment.
  • various factors can influence the actual effective amount used for a particular application.
  • the severity of a SARS-CoV-2 virus infection e.g., COVID-19
  • the route of administration e.g., the route of administration, the age and general health condition of the mammal, excipient usage, the possibility of co-usage with other therapeutic or prophylactic treatments such as use of other agents (e.g., antiviral agents such as remdesivir (e.g., VEKLURY ® ), galidesivir, and/or favipiravir (e.g., AVIGAN ® ), and antibody based treatments such as convalescent human plasma therapy and/or human plasma-derived product therapy), and the judgment of the treating physician may require an increase or decrease in the actual effective amount of one or more SARS-CoV-2 polypeptides provided herein (and/or
  • an effective amount of one or more SARS-CoV-2 polypeptides provided herein is about 0.1 pg, 0.2 pg, 0.3 pg, 0.4 pg, 0.5 pg, 0.6 pg, 0.7 pg, 0.8 pg, 0.9 pg, 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9mg, or 10 mg.
  • an effective frequency of administration of one or more SARS-CoV-2 polypeptides provided herein can be a frequency that induces or increases an immune response against a coronavirus such as SARS- CoV-2 within the mammal (e.g., a human) without producing significant toxicity to the mammal.
  • an effective frequency of administration of one or more SARS-CoV-2 polypeptides provided herein can be from about one to about three administrations.
  • the frequency of administration of one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein) can remain constant or can be variable during the duration of treatment. Various factors can influence the actual effective frequency used for a particular application.
  • the severity of a SARS-CoV-2 virus infection when treating a mammal having such an infection, the route of administration, the age and general health condition of the mammal, excipient usage, the possibility of co-usage with other therapeutic or prophylactic treatments such as use of other agents (e.g., antiviral agents such as remdesivir (e.g., VEKLURY ® ), galidesivir, and/or favipiravir (e.g., AVIGAN ® ), and antibody based treatments such as convalescent human plasma therapy and/or human plasma-derived product therapy), and the judgment of the treating physician may require an increase or decrease in the actual effective frequency of administration of one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein).
  • agents e.g., antiviral agents such as remdesivir (e.g., VEKLURY ® ), galides
  • an effective duration of administration of one or more SARS-CoV-2 polypeptides provided herein can be a duration that induces or increases an immune response against a coronavirus such as SARS-CoV-2 within the mammal (e.g., a human) without producing significant toxicity to the mammal.
  • an effective duration of administration of one or more SARS-CoV-2 polypeptides provided herein can vary from a single time point of administration to several weeks (e.g., 2, 3, or 4 weeks) to several months (e.g., 2 or 3 months). Multiple factors can influence the actual effective duration used for a particular application.
  • the severity of a SARS-CoV-2 virus infection when treating a mammal having such an infection, the route of administration, the age and general health condition of the mammal, excipient usage, the possibility of co-usage with other therapeutic or prophylactic treatments such as use of other agents (e.g., antiviral agents such as remdesivir (e.g., VEKLURY ® ), galidesivir, and/or favipiravir (e.g., AVIGAN ® ), and antibody based treatments such as convalescent human plasma therapy and/or human plasma-derived product therapy), and the judgment of the treating physician may require an increase or decrease in the actual effective duration of administration of one or more SARS-CoV-2 polypeptides provided herein (and/or nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein).
  • agents e.g., antiviral agents such as remdesivir (e.g., VEKLURY ® ), galides
  • a mammal e.g., a human
  • a mammal can be administered a first dose.
  • the mammal can be administered a second dose.
  • the second dose is administered about 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 40 days,
  • a mammal is administered another dose about 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days,
  • a mammal is administered a total of two doses, three doses, four doses, five doses, six doses, seven doses, eight doses, nine doses, or ten doses.
  • the mammal can be administered another round of vaccinations with the same vaccine composition or with a vaccine composition having a different polypeptide or set of polypeptides (and/or nucleic acid encoding a different polypeptide or set of polypeptides).
  • a mammal is administered with a dose with the same vaccine composition as a previous dose, or with a vaccine composition having a different polypeptide or set of polypeptides (and/or nucleic acid encoding a different polypeptide or set of polypeptides) as a previous dose, after a fixed time interval, e.g., 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, or 24 months.
  • a fixed time interval e.g., 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, or 24 months.
  • a mammal is administered with a dose with the same vaccine composition as a previous dose, or with a vaccine composition having a different polypeptide or set of polypeptides (and/or nucleic acid encoding a different polypeptide or set of polypeptides) as a previous dose, after it has been determined that immune response against SARS-CoV-2 has decreased.
  • a mammal e.g., a human
  • a mammal is administered a dose of one or more SARS- CoV-2 polypeptides provided herein (e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87), after the mammal has received a different vaccine for SARS-CoV-2.
  • SARS- CoV-2 polypeptides provided herein e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87
  • a mammal e.g., a human
  • a mammal is administered a dose of one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87), where the mammal has not received a different vaccine for SARS-CoV-2 previously.
  • SARS-CoV-2 polypeptides provided herein e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87
  • examples of other vaccines for SARS-CoV-2 include, but are not limited to the Pfizer-Biontech COMIRNATY, and the Modema Spikevax.
  • a mammal e.g., a human
  • a mammal is administered a dose of one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87), before the mammal has received another vaccine for SARS-CoV- 2
  • kits containing one or more e.g., one, two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more
  • SARS-CoV-2 polypeptides provided herein e.g., one or more substantially pure polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1- 87
  • nucleic acid encoding one or more SARS-CoV-2 polypeptides provided herein e.g., nucleic acid encoding one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87.
  • kits provided herein can include one or more of the polypeptides set forth in Tables 1, 2, 3, and 4.
  • a kit provided herein can also be used for diagnosis of SARS-CoV-2 infection.
  • a kit provided herein can also be used for monitoring immune response to the COVID-19 vaccines provided herein or by others. The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.
  • This example describes the identification of immunogenic SARS-CoV-2-derived polypeptides.
  • Human cell lines (such as Caco-2, A549, and THP-1) are infected with live SARS-CoV- 2 virus (Wuhan/Washington USA/WA1-F6 strain).
  • SARS-CoV-2-derived polypeptides are identified using strong cation exchange (SCX) chromatography and are analyzed by liquid chromatographic tandem mass spectrometry (LC- MS/MS).
  • SCX strong cation exchange
  • LC- MS/MS liquid chromatographic tandem mass spectrometry
  • the identified polypeptides have HLA class I and class II high polypeptides binding properties (IC50).
  • Polypeptides having HLA class I binding properties are 8-12 amino acid sequences long.
  • Polypeptides having HLA class II binding properties are 13-25 amino acid sequences long.
  • S GenBank accession: QHD43416)
  • M QHD43419)
  • E QHD434128
  • Epitope probability scores are calculated for each amino acid residue using a threshold of 0.35 (corresponding to > 0.75 specificity and sensitivity below 0.5), and only epitopes > 5 amino acid residues in length are further analyzed.
  • the structure of the SARS-CoV-2 S protein is accessed from the Protein Data Bank (PDB ID: 6VSB).
  • Discontinuous (i.e., structural) B cell epitope predictions for the S protein structure are carried out using DiscoTope 1.1 with a score threshold greater than - 7.7 (corresponding to > 0.75 specificity and sensitivity below 0.5).
  • the main protein structure is modeled in PyMOL (Schrodinger, LLC), with predicted B cell epitopes identified by both BepiPred 1.0 and DiscoTope 1.1 highlighted as spheres.
  • PBMCs Peripheral blood mononuclear cells
  • BD BD Biosciences, San Jose, CA
  • ELISPOT kit according to the manufacturer’s instructions.
  • PBMCs Frozen PBMCs are thawed according to established laboratory procedure and plated at 2x10 5 cells/well in a 96-well BDTM ELISPOT plates coated with anti-human IFN-gamma antibody.
  • Cells are treated with one of the following conditions: RPMI culture media with 5% FBS Penicillin/Streptomycin (CM) for the unstimulated/negative control condition; pooled SARS-CoV-2 peptides (at 10 pg/mL final concentration of each individual peptide) or whole Spike SI, RBD and Nucleocapsid proteins (at 1.25 pg/mL final concentration).
  • CM Penicillin/Streptomycin
  • Phytohemagglutinin (PHA) at 5 pg/mL is used as a positive control. Samples stimulated with each of the listed conditions are tested in quadruplicate. Cells are incubated at 37°C, 5% CO2 for 18-20 hours. The plates are developed, and immune responses are quantified using the BDTM human IFN-g ELISPOT kit. All plates are scanned and analyzed using the same scanning and counting parameters on ImmunoSpot® S6 Macro Analyzer (Cellular Technology Ltd., Cleveland, OH, USA) using the ImmunoSpot® 5.1 Professional software.
  • Peptide pools are considered positive if all of the following criteria are met: (i) the average spot count [stimulated- unstimulated] >4.99, (ii) the fold-change [stimulated compared to unstimulated] >1.99, and (iii) the t-test p-value ⁇ 0.05.
  • PBMCs are plated at 2x10 5 cells/well in a 96-well BDTM ELISPOT plates coated with anti-human IFN-g antibody.
  • Cells are treated with one of the following conditions in quadruplicate: CM (unstimulated/negative control), or individual SARS-CoV-2 peptides at 10 pg/mL final concentration.
  • CM unstimulated/negative control
  • PHA 5 pg/mL
  • Cells are incubated at 37°C, 5% CO2 for 18-20 hours. The plates are developed, and immune responses are quantified using the BDTM human IFN-g ELISPOT kits.
  • Naturally processed and in silico predicted HLA I and II SARS-CoV-2 peptides are identified through mass spectrometry and binding affinity prediction algorithms, as well as by generating overlapping 15-mers peptides from the structural (S, N, M, E) proteins. A total of 397 peptides are initially identified. These 397 peptides are grouped into three sets of 95 peptides (Sets # 1, 2, and 4) and one set of 111 peptides (Set #3). Each set of peptides is further analyzed using the same IFN-g ELISPOT assay protocol as described above.
  • FIG. 1A depicts representative ELISPOT response of peptide pools to plasma from convalescent subjects. For example, FIG.
  • IB depicts IFN-g ELISPOT response to pools 1-19 of subject 30, showing positive responses from peptide pools 4 and 15. Positive peptide pools are further analyzed at the individual peptide level. Based on the number of responders (3/3 criteria in at least 2 subjects) as well as spot forming units (SFUs) per 200,000 PBMCs (reflective of the magnitude of the T cell response), six pools (#2, 4, 8, 15, 16, 19) from Set #1 are selected for further individual peptide testing. Similarly, sixteen peptide pools from Set #2, sixteen peptide pools from Set #3, and twelve peptide pools from Set #4 are selected.
  • SFUs spot forming units
  • FIG. 2A-C depict representative IFN-g ELISPOT response to individual peptides from convalescent plasma from Subjects 17, 30, and 52 respectively.
  • the selection is also expanded by adopting a less stringent selection criterion for maximal sensitivity, to include all peptides that meet the three criteria for positive response in at least one convalescent subject. This results in the inclusion of 18 additional peptides, yielding a total of 53 peptides (Table 1, SEQ ID NOs: 1-53) that are selected for large-scale synthesis and further testing in golden Syrian hamsters.
  • PVDF poly vinylidene fluoride
  • Cells are treated with one of the following conditions: RPMI culture media with 10% FBS, 0.1 mM non-essential amino acids, 0.5 mM sodium pyruvate, 0.05 mM 2-mercaptoethanol and Penicillin/Streptomycin, (unstimulated/negative control); individual SARS-CoV-2 peptide at 10 pg/mL final concentration, or 1.25 pg/mL Spike SI and Nucleocapsid proteins.
  • Concanavalin A (Con A) (2 pg/ml) or phytohemaggluttin (PHA) (2 pg/ml) are used as positive control. Samples stimulated with each of the conditions are tested in quadruplicate.
  • Example 2 Vaccinating Agains t SARS-Co V-2 in hams ters
  • Hamsters have been an animal model of choice to study SARS-CoV-2 infection due to the fact that clinical disease and pathologic features of infection closely resemble those found in human COVID-19 patients.
  • hamster ACE2 interacts well with SARS-CoV-2, thus hamster cells are natively susceptible to infection and do not require viral adaptation to the animal or transgenic expression of human ACE2.
  • severe lung injury in hamsters occurs after infection and the degree of lung pathology is associated with infectious dose, much like in human disease.
  • lung abnormalities in hamsters include severe, bilateral, multi-lobular ground glass opacity and regions of lung consolidation, similar to that found in human disease.
  • mice cells are not natively susceptible to infection therefore a variety of models have been developed.
  • the most common models include: genetically modified mice expressing human ACE, the use of mouse-adapted SARS-CoV-2, temporary transduction of hACE into the mouse respiratory tract using adenovirus or adeno- associated viruses.
  • mice Female golden Syrian hamsters (Charles River Laboratories, Wilmington, MA) are immunized with a 2-dose regimen with a 14-day interval between doses. Two weeks after the second dose, hamsters are euthanized. Hamster blood is collected by cardiac puncture and serum is prepared for the quantification of peptide-specific antibodies by an in-house indirect ELISA method. Spleens and draining lymph nodes serve as a source of cells for the IFN-g ELISPOT and other assays. Unless otherwise noted, water-in-oil emulsions are administered subcutaneously, all other adjuvant formulations are administered intramuscularly.
  • a total of 52 peptides are tested for immunogenicity. These peptides are divided into five groups, as shown in FIG. 5A-E, and formulated with CFA and CpG as indicated in FIG. 4. Antibody responses in hamster sera specimens to individual peptides or peptide pools are quantified by ELISA. Briefly, Immulon 4 HBX 96-well plates for ELISA are obtained from Thermo Fisher Scientific (Waltham, MA). The plate is coated with 1 pg/well of either a pool of peptides or individual peptides in coating buffer (50 mM sodium carbonate, pH 9.6) overnight at 4°C.
  • coating buffer 50 mM sodium carbonate, pH 9.6
  • the plate is blocked with 2% BSA in PBS for 1 hour at room temperature, followed by washing three times with 0.5% Tween in PBS (PBST).
  • Sera are diluted 1:200 in PBS and added to each well and the plate is incubated for 2 hours at room temperature. After incubation, the plate is washed three times with PBST.
  • the secondary antibody is conjugated with HRP, and iss added at a 1 : 10,000 dilution in PBS. The plate is incubated for 1 hour at room temperature.
  • TMBE-100 peroxidase substrate Rockland Immunochemicals, Inc., Limerick, PA
  • Optical density at 450 nm (OD450) is read within 15 minutes after adding H2S04 using a Spectramax® ABS Plus microplate reader (Molecular Devices, San Jose, CA) and the SoftMax® 7 Pro Software.
  • Peptide-specific antibodies in each hamster are quantified in quadruplicate wells with the average response is plohed on FIGS. 5A-E.
  • the dashed line represents the threshold for defining a positive response - a signal-to-noise ratio of 3.
  • many of the screened peptides induces the generation of peptide-specific antibody responses of varying magnitudes in immunized hamsters.
  • FIG. 7 A summary of peptide-specific antibody titers (as measured by ELISA) and T cell responses (as measured by IFN-g ELISPOT) of selected peptides is shown in FIG. 7.
  • a total of 52 peptides are tested for immunogenicity. These peptides are divided into five groups, as indicated in FIG. 6A-E, and are formulated with CFA and CpG as indicated in FIG. 4. Antibody responses in hamster sera specimens to individual peptides or peptide pools are quantified by IFN-g ELISPOT assay.
  • a MabtechTM hamster-specific IFN-g ELISPOT assay is performed similar to that as described above for human PBMC testing (Example 1).
  • Concanavalin A (ConA) (10 pg/mL) is used as a positive control (stimulated condition) instead of PHA as it has been shown to perform well as a positive control in hamster cell-based assays.
  • Cell culture media is used as the unstimulated (“unstim”) condition. The remaining conditions (cells/well, incubation times, antigen concentrations) are identical to those reported above in Example 1.
  • FIG. 6A-E The results are shown in FIG. 6A-E, and demonstrate that many of the selected peptides are immunogenic in hamsters, eliciting T cell responses of varying magnitude. Based on these immunogenicity experiments, five exemplary peptides (M2, M3, N7, S3, and ORF-3a) are selected for further testing.
  • Table 6 List of adjuvants used to test 5 exemplary peptides
  • FIGS. 8A-H and FIGS. 9A-H The results are shown in FIGS. 8A-H (IgG ELISA) and FIGS. 9A-H (IFN-g ELISPOT).
  • the adjuvant combinations tested showed varying levels of immunogenicity, with water-in-oil emulsions (e.g., CFA and the Montanides) exhibiting stronger adjuvant activity, followed by oil-in- water emulsions (e.g., Addavax, AddS03, and EmT4).
  • TLR and RLR agonists e.g., CpG, Poly I:C, T4, RIG-I agonist
  • T cell epitopes appear to induce a robust antibody response, while others induce a robust T cell response, and a number of peptides induce both antibody and T cell responses.
  • mice Male C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME) in groups of 5 mice are subcutaneously or intramuscularly immunized with a two-dose regimen with a 14-day, 21-day or 28-day interval between vaccine doses. Each mouse receives a single peptide, a pool of selected peptides or a recombinant protein formulated with different adjuvants and/or delivery systems. Mice are euthanized 14 days after the second dose. Mouse blood is collected from euthanized mice by cardiac puncture and serum is prepared by centrifugation at 3000xg for 15 minutes at 4°C then stored at -80°C for further analyses. Draining lymph nodes and spleens are harvested and a single cell lymphocyte suspension is prepared for IFN-g ELISPOT assays. Pooled screening of peptides in combination with CpG and CFA
  • mice are immunized as described in the method section detailed immediately above with 52 peptides (listed in Table 1, with the exception of M9) adjuvanted with CpG and CFA (IFA is used for the boost vaccination as recommended).
  • the 52 peptides are divided into 6 groups (MAI to MA6) of 5.
  • Groups MAI to MA6 are subcutaneously immunized with a combination of 9-10 peptides that include peptides from spike (S), nucleocapsid (N), membrane (M) and open reading frame (ORF) proteins from SARS- COV-2.
  • Groups MA7, MA8, and MA9 are designated as control groups and are immunized with CpG+CFA/IFA only, S protein (20 pg), and N protein (20 pg), respectively.
  • FIGS. 10A-I antibody titers as measured by ELISA
  • FIGS. 11A-I T cell responses as measured by IFN-g ELISPOT.
  • twelve peptides elicit detectable antibody responses and seven peptides elicited T cell responses in mice. Three of these peptides elicit both antibody and T cell responses. Twelve of these peptides are also immunogenic in hamsters.
  • Table 8 shows the top 10 immunogenic peptides in mice and hamsters. Peptides are ranked based on magnitude of responses in arbitrary antibody units (a.u.) and counts of Spot Forming Units (SFU/200,000 cells) as measured by IFN-g ELISPOT and antibody ELISA assays, respectively.
  • mice are divided into 4 groups of 5 (MB1 to MB4, as in Table 9 below).
  • Group MB1 is primed with 10 selected peptides (20 pg) combined with CpG + CFA, and is boosted with the same peptide formulation with CpG + IFA after 21 days.
  • Group MB2 is immunized with the identical formulation at an interval of 28 days between the doses.
  • Groups MB3 and MB4 are prime-boosted with SARS-CoV-2 S protein combined with CFA/IFA + CpG at 21-day and 28- day intervals, respectively. Immunogenicity is assessed using IFN-g ELISPOT and antibody ELISA as described in Examples 2 and 3.
  • Results are shown in FIG. 13.
  • the top panels of FIG. 13 depict antibody titers as measured by ELISA while the bottom panels of FIG. 13 depict T cell responses as measured by IFN-g ELISPOT, induced by either the ten peptides or the spike protein, given twice at dose intervals of 21 or 28 days.
  • the results indicate that a 28-day interval between prime and boost immunization elicits significantly more robust immune responses to peptides in mice.
  • mice Experiments are performed to identify the peptide-adjuvant combinations eliciting the strongest immune responses in mice.
  • mice are divided into 4 groups of 5 (MCI to MC4) and are immunized via the subcutaneous (s.c) route with two doses of a formulation of 10 peptides (Table 10) combined with different adjuvants and TLR4 agonist GLA, at a 28-day interval.
  • Group MCI is immunized with peptides combined with water-in-oil emulsion Montanide 51 + GLA;
  • Group MC2 is administered 10 peptides + Alum + GLA;
  • Group MC3 receives 10 peptides + EmT4 + GLA and group MC4 is immunized with 10 peptides + squalene-based oil-in-water emulsion Addavax + GLA.
  • the mice are euthanized 14 days after the second dose and immune responses are assessed using IFN-g ELISPOT and antibody ELISA as described in Examples 2 and 3.
  • Results are shown in FIG. 14.
  • the top panels of FIG. 14 depict antibody titers as measured by ELISA while the bottom panels of FIG. 14 depict T cell responses as measured by IFN-g ELISPOT, induced by a combination of ten peptides formulated with different adjuvants.
  • the results indicate that adjuvants have variable effects on immunogenicity, with water-in-oil emulsion adjuvants inducing superior immune responses, followed by oil-in-water emulsions.
  • TLR4 agonist is shown to boost immunogenicity.
  • Example 6 Testing the immunogenicity of elongated peptides in mice
  • each peptide included in the set of 10 peptides described in Examples 4 and 5 is elongated by extending the amino acid sequence on both the N- and C- termini to make a 40 amino acid long peptide, reflecting the natural SARS-CoV-2 sequence (Table 11).
  • Each of the long peptides includes the full sequence of the respective short peptide in bold.
  • mice are divided into 13 groups of 5 (Table 12).
  • Groups MD1 to MD10 are primed with a single long peptide (100 pg) formulated with CpG + CFA and boosted with the same peptide combined with CpG + IFA after 28 days.
  • Group MD11 is immunized with a single N overlap peptide containing the sequence of nine individual Nucleocapsid protein-derived peptides (N3, N4, N5, N6, N7, N23, N13, N16, N18) within its sequence.
  • Group MD12 is immunized with a pool of all 10 long peptides formulated with CFA/IFA + CpG.
  • Group MD13 is immunized with an equal molar concentration of short S14 and S15 peptides for comparison with group MD4, which is immunized with S14 long peptide (spanning both S14 and S15 short sequences). This comparison allows us to assess whether or not the differences in flanking amino acid sequences affect immunogenicity.
  • the mice are euthanized 14 days after the second dose and immune responses are assessed using IFN-g ELISPOT and antibody ELISA, as described in Example 3.
  • mice T cell production of IL-4 is measured.
  • a BDTM mouse- specific IL-4 ELISPOT assay is performed on single cell suspensions similar to the mouse- specific IFN-g ELISPOT assay.
  • PMA/Ionomycin (81 nM/1.34 mM) is used as a positive control due to its superior performance to PHA and concanavalin A in IL-4 detection assays.
  • the remaining conditions (cells/well, incubation times, antigen concentrations) are identical to those reported above for IFN-g ELISPOT assays.
  • Mouse immune response is also measured with a pseudovirus/rVSV microneutralization assay.
  • neutralizing antibody response is assessed using a high-throughput, fluorescence/GFP-based pseudo virus/VSV microneutralization assay, developed in-house to allow for rapid imaging and quantification of cell infection with the ImageXpress® platform/software (Molecular Devices).
  • the assay is based on a replication-competent VSV virus expressing eGFP and the SARS-CoV-2 Spike protein (Wuhan-Hu-1) in place of the native envelope glycoprotein.
  • Serial two-fold dilutions are performed from 1: 10 up to 1:5,120 (four replicate wells per dilution step) and mixed with an equal volume of tissue culture media/DMEM medium containing 5% FCS and Penicillin/Streptomycin, containing 3,000 PFUs of rVSV-SARS-CoV-2-S virus per well, in a 96-well microplate.
  • the final serum dilutions for neutralization are 1:20 up to 1:10,240.
  • Sera and virus mixtures are incubated for 1 hour at 37°C at 5% C02.
  • each testing batch includes a pooled positive control serum, a pooled negative control serum and a human monoclonal neutralizing antibody (IgGl; Active Motif, catalog number 91361).
  • IgGl human monoclonal neutralizing antibody
  • the coefficient of variation/CV of this assay based on repeated control measurements run on different days is 7.38%.
  • the antibody ELISA is performed using different dilutions of mouse sera.
  • Group MD4 is tested at a 1:250 dilution. All other groups are diluted until antibody responses are no longer saturated. As a results, an extended range of dilutions is tested (FIG. 18).
  • FIGS. 15-19 depict peptide-specific antibody titers induced by individual long peptides, as measured by ELISA.
  • FIG. 16 depicts peptide-specific T cell responses induced by individual long peptides, as measured by IFN-g ELISPOT. A summary of these responses are shown in FIG. 17. As shown in FIG. 18, huge antibody responses are induced. For example, samples from MD7 and MD8 are still saturated even at dilutions of 1 :20,000. Further experiments are needed to at higher dilutions to determine antibody titer levels accurately. Regardless, it is clear that a strong antibody response is induced by the long peptides.
  • FIG. 19 depicts the neutralization activity of peptide-specific antibody induced by individual long peptides in MD experiment, as measured by the pseudo virus/rVSV microneutralization assay.
  • Sera from mice of MA7 group (mice immunized with CFA/IFA + CpG but no peptides; Example 3, Table 6) are included as a negative control.
  • Asterisks (*) indicate a significant difference in neutralization activity in sera from peptide- vaccinated mice and control mice. Further experiments will be performed to adjust the neutralizing antibody assay protocol to reduce non-specific background like that observed in group MD11.
  • long peptides generally elicit significantly superior immune responses as compared to short peptides across the immunogenicity assays. Immunization with long peptides is shown to elicit production of binding as well as neutralizing antibodies capable of recognizing full protein sequences. Induction of strong T cell responses is also observed.
  • Example 7 Testing the immunogenicity of peptides delivered in virus-like particles ( VLPs ) in mice
  • VLPs virus-like particles
  • VLPs are nanostructures with diverse applications in immunization, therapeutics, and diagnostics.
  • VLPs possess self-adjuvanting properties and decorating them with individual selected peptides (Table 13) on the surface allows for highly repetitive presentation of over 170 epitopes.
  • VLPs are easier than emulsions to administer by various routes.
  • VLP1 to VLP6 Six sets of peptide-VLP combinations labeled VLP1 to VLP6 are created with SI, S9, M8, N7, N15 or ORF3a peptides, respectively. Each VLP is formulated with one type of peptide only.
  • mice of ME7 groups are immunized subcutaneously with empty VLPs while mice of ME8 are immunized with a mixture of all 6 peptide-loaded VLPs.
  • Each animal receives a total of 100 pL (containing 20 pg) of the VLP formulation subcutaneously (50 pL in each flank) as a two-dose regimen at a 28-day interval. The mice are euthanized 14 days after the second dose.
  • Immunogenicity is assessed as described in Examples 4-6, using IFN-g ELISPOT, IL-4 ELISPOT, antibody ELISA and pseudo virus/rVSV microneutralization assay.
  • the immunogenicity results of the selected peptides in VLP (VLP-peptide) and non-VLP formulations are compared.
  • Results are shown in FIGS. 20-26. Results show that VLP+peptide combinations elicit equivalent or stronger T and B cell response than peptides formulated with CFA/IFA + CpG, and require 5%-10% of the antigen dose when compared to CFA/IFA + CpG adjuvanted formulations (Table 14). IL-4 ELISPOT responses are shown to be much lower (and undetectable in some groups) than IFN-g ELISPOT responses across the experiments, suggesting a Thl -biased immune response.
  • mice are divided into 4 groups (MF1 to MF4) and receive (i) no protein or peptide, (ii) a set of 6 peptides (20 pg each), (iii) recombinant SARS-CoV-2 RBD protein (20 pg) or (iv) 6 peptides combined with SARS-CoV-2 RBD protein (20 pg each) as a two-dose regimen at a 28 day interval (Table 15). Mice are euthanized 14 days after the second dose and immunogenicity assays are performed as described as in Examples 4-7.
  • Table 15 Comparing immunogenicity of RBD and peptides As shown in FIG. 27, immunization with SARS-CoV-2 RBD and a combination of peptides elicit robust antibody responses to the RBD protein. T cell responses to SARS-CoV-2 RBD antigen are negligible.
  • Hamsters are subsequently challenged with live SARS-CoV-2 virus.
  • Example 9 Comparison of dose intervals of long peptides in mice Experiments are performed to test whether varying the intervals between the first and second vaccine doses enhance the immune response to long peptides when combined with CFA/IFA + CpG in mice.
  • mice are divided into groups, primed with selected long peptides (see Example 6) combined with CpG + CFA, and boosted with the same long peptide formulation with CpG + IFA after 21 days.
  • a second group of mice are immunized with the identical formulation at an interval of 28 days between the doses.
  • Two control groups are primed and boosted with SARS- CoV-2 S protein combined with CFA/IFA + CpG at 21 -day and 28-day intervals, respectively.
  • Immunogenicity are assessed using IFN-g ELISPOT and antibody ELISA as described in Examples 2 and 3.
  • long peptides are tested in combination with different adjuvants previously shown to augment immunogenicity of shorter peptides (see Example 5).
  • Long peptides are tested with Montanide 51 + TLR4 agonist, Alum, Alum + TLR4 agonist, EmT4 + TLR4 agonist, and Addavax + TLR4 agonist. Additional adjuvants are also tested.
  • mice are divided into groups and are immunized with two doses of a formulation of different long peptides combined with different adjuvants and TLR4 agonist GLA, at a 28-day interval.
  • the mice are immunized with peptides combined with water-in-oil emulsion Montanide 51 + GLA;
  • Group MC2 is administered 10 peptides + Alum + GLA;
  • Group MC3 receives 10 peptides + EmT4 + GLA and group MC4 is immunized with 10 peptides + squalene- based oil-in-water emulsion Addavax + GLA.
  • the mice are euthanized 14 days after the second dose and immune responses are assessed as described above in Example 7, using IFN-g ELISPOT, IL-4 ELISPOT, antibody ELISA and pseudovirus/rVSV microneutralization assay.
  • Peptide-VLP combinations are created with selected long peptides. Each VLP is formulated with one type of peptide only. Negative controls are also performed with mice immunized with empty VLPs. A group of mice are immunized with a mixture of peptide-loaded VLPs. Each animal is immunized with a two-dose regimen at a 28-day interval. The mice are euthanized 14 days after the second dose. Immunogenicity is assessed as described in Example 7, using IFN-g ELISPOT, IL-4 ELISPOT, antibody ELISA and pseudovirus/rVSV microneutralization assay. The immunogenicity results of the selected peptides in VLP (VLP- peptide) and non-VLP formulations (peptide + CFA/IFA + CpG).
  • Example 12 Challenge experiments in hamsters and mice
  • hamsters are grouped, and each group receives a two-dose regiment of either short peptides + CFA/IFA + CpG, long peptides + CFA/IFA + CpG, N protein + CFA/IFA + CpG, S protein + CFA/IFA + CpG, or DMSO + CFA/IFA + CpG (negative control).
  • the hamsters are challenged 14 days after the second dose of vaccine, with 50,000 viral particles of SARS-CoV-2 administered intranasally. Viral load in feces is quantified on days 2, 5, and 7. The nasal viral load is quantified daily by a nasal wash.
  • Serum is collected from the hamsters to monitor the immune response before the first dose of vaccine, before the second dose of vaccine, before challenge, and at euthanasia.
  • the immune response is measured by quantifying the neutralizing and IgG antibody levels, S protein binding levels, RBD binding levels, using peptide antibody ELISAs. Pseudo-virus neutralization assays are also performed.
  • the hamsters are euthanized 3 or 7 days after infection and the brain and lung tissues are harvested. The tissues are homogenized and the viral load in each tissue is quantified by qRT-PCR, while the number of infectious virus particles is quantified by a Median Tissue Culture Infectious Dose (TCID50) assay.
  • Blood and lymph nodes are collected at euthanasia to test T-cell response to vaccine peptides using IFN-g ELISPOT.
  • Example 13 Comparison with a vaccine of proven efficacy in hamsters and mice
  • hamsters are immunized intramuscularly with 100 pL (6 pg RNA) of Pfizer/BioNTech’s SARS-CoV-2 mRNA vaccine (BNT162b2) with a two-dose regimen at a 21- day interval. Immune responses is studied at 14 days and 28 days after the second vaccine dose. A negative control group of hamsters is immunized with saline diluent. Experimental groups are described in Table 16. Results are provided in Figure 28. Table 16: Evaluating immunogenicity of Pfizer mRNA vaccine in hamsters
  • mice are immunized intramuscularly with 100 pL (6 pg RNA) of Pfizer/BioNTech’s SARS-CoV-2 mRNA vaccine (BNT162b2) with a two-dose regimen at a 21-day interval. Immune responses is studied at 14 days and 28 days after the second vaccine dose. A negative control group of mice is immunized with saline diluent. Experimental groups are described in Table 17. Results are provided in Figure 29.
  • Example 15 Treating SARS-CoV-2 A human identified as needing an induction or an increase in an immune response against a SARS-CoV-2 infection (e.g., COVID-19) such as a human having or at risk of developing COVID-19 is administered one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87).
  • the administered polypeptide(s) can prevent the development of one or more symptoms of COVID-19.
  • a human identified as needing an induction or an increase in an immune response against a SARS-CoV-2 infection e.g., COVID-19
  • a human having or at risk of developing COVID-19 is administered one or more SARS-CoV-2 polypeptides provided herein (e.g., one or more SARS-CoV-2 polypeptides that comprise, consist essentially of, or consist of the amino acid sequence set forth in any of SEQ ID NOs: 1-87).
  • the administered polypeptides(s) can reduce the severity of or eliminate one or more symptoms of COVID-19.
  • Embodiment 1 A substantially pure polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • Embodiment 2. A composition comprising the substantially pure polypeptide of embodiment 1.
  • Embodiment 3 A composition comprising at least two polypeptides, wherein each of said at least two polypeptides is a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • Embodiment 4 The composition of any one of embodiments 2-3, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:5, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:40.
  • Embodiment 5 The composition of any one of embodiments 2-3, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:21, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:46.
  • Embodiment 6 The composition of any one of embodiments 2-3, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:44, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:45.
  • Embodiment 7 The composition of any one of embodiments 2-3, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:3, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 16, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:28, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:31, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37.
  • composition of any one of embodiments 2-3 wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 17, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:24, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 43.
  • Embodiment 9 The composition of any one of embodiments 2-3, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 8, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 10, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 11, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19.
  • Embodiment 10 The composition of any one of embodiments 2-3, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:43, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:53, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:38, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:34, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18.
  • Embodiment 11 The composition of any one of embodiments 2-3, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:72, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 77, and a polypeptide consisting of the amino acid sequence
  • Embodiment 12 The composition of any one of embodiments 2-3, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 78.
  • Embodiment 13 The composition of any one of embodiments 2-12, wherein said composition comprises an adjuvant or an immunostimulatory molecule.
  • Embodiment 14 The composition of embodiment 13, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • Embodiment 15 The composition of embodiment 13, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 to
  • Embodiment 16 The composition of embodiment 13, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG- I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • Embodiment 17 The composition of any one of embodiments 2-12, wherein said polypeptides are attached to one or more virus-like particles (VLP).
  • VLP virus-like particles
  • Embodiment 18 The composition of embodiment 17, wherein said VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • Embodiment 19 The composition of embodiment 17, wherein said VLPs are made from Q-beta bacteriophage.
  • Embodiment 20 A composition comprising nucleic acid encoding a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs:l-87.
  • Embodiment 21 A composition comprising nucleic acid encoding at least two polypeptides, wherein each of said at least two polypeptides is a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87.
  • Embodiment 22 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:5, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:40.
  • Embodiment 23 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:21, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:46.
  • Embodiment 24 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:44, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:45.
  • Embodiment 25 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:3, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 16, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:28, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:31, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:37.
  • Embodiment 26 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:9, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 17, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:24, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:27, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 43.
  • Embodiment 27 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 8, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 10, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 11, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 14, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 19.
  • Embodiment 28 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 12, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 13, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 25, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:43, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:53, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:38, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 15, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:39, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:34, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 18.
  • Embodiment 29 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:72, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 77, and a polypeptide consisting of the amino acid
  • Embodiment 30 The composition of any one of embodiments 20-21, wherein said composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 70, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:71, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:73, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:74, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:75, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:76, a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:77, and a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 78.
  • Embodiment 31 The composition of any one of embodiments 20-30, wherein said composition comprises an adjuvant or an immunostimulatory molecule.
  • Embodiment 32 The composition of embodiment 31, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene
  • Embodiment 33 The composition of embodiment 31, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid- inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 to
  • Embodiment 34 The composition of embodiment 31, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03-like, AS04-like, ASOlB-like, GM-CSF, retinoic acid-inducible gene I (RIG- I), lipid nanoparticles (e.g., LION), and GLA.
  • a water in oil emulsion e.g., Montanide 720, Montanide 51
  • TLR4 toll-like receptor 4
  • Embodiment 35 The composition of any one of embodiments 20-32, wherein said polypeptides are attached to one or more virus-like particles (VLP).
  • VLP virus-like particles
  • Embodiment 36 The composition of embodiment 35, wherein said VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • Embodiment 37 The composition of embodiment 35, wherein said VLPs are made from Q-beta bacteriophage.
  • Embodiment 38 The composition of any one of embodiments 20-32, wherein said nucleic acid is in the form of a non-viral vector.
  • Embodiment 39 The composition of embodiment 38, wherein said non-viral vector is an expression plasmid.
  • Embodiment 40 The composition of any one of embodiments 20-32, wherein said nucleic acid is in the form of a viral vector.
  • Embodiment 41 The composition of embodiment 40, wherein said viral vector is selected from the group consisting of a vector based on an adenoviruses, a vector based on an adeno-associated virus (AAV), a vector based on an retrovirus, a vector based on an lentivirus, a vector based on a measles virus, a vector based on a vesicular stomatitis virus, and a vector based on vaccinia virus.
  • AAV adeno-associated virus
  • Embodiment 42 A method for increasing an immune response against a coronavirus in a mammal, wherein said method comprises administering to said mammal a composition comprising a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87 or nucleic acid encoding said polypeptide.
  • Embodiment 43 The method of embodiment 42, wherein said mammal is a human.
  • Embodiment 44 The method of any one of embodiments 42-43, wherein said coronavirus is a severe acute respiratory distress coronavirus 2 (SARS-CoV-2).
  • SARS-CoV-2 severe acute respiratory distress coronavirus 2
  • Embodiment 45 The method of any one of embodiments 42-44, wherein said composition comprises an adjuvant or an immunostimulatory molecule.
  • Embodiment 46 The method of embodiment 45, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • Embodiment 47 The method of any one of embodiments 42-46, wherein at least two doses of said composition are administered.
  • Embodiment 48 The method of any one of embodiments 42-46, wherein two doses of said composition are administered.
  • Embodiment 49 The method of any one of embodiments 42-48, wherein said polypeptide is presented on one or more virus-like particles (VLP).
  • VLP virus-like particles
  • Embodiment 50 The method of embodiment 49, wherein said VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • Embodiment 51 The method of embodiment 49, wherein said VLPs are made from Q- beta bacteriophage.
  • Embodiment 52 A method for treating a mammal at risk of developing a coronavirus infection, wherein said method comprises administering to said mammal a composition comprising a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87 or nucleic acid encoding said polypeptide.
  • Embodiment 53 The method of embodiment 52, wherein said mammal is a human.
  • Embodiment 54 The method of any one of embodiments 52-53, wherein said coronavirus infection is COVID-19.
  • Embodiment 55 The method of any one of embodiments 52-54, wherein said composition comprises an adjuvant or an immunostimulatory molecule.
  • Embodiment 56 The method of embodiment 55, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • Embodiment 57 The method of any one of embodiments 52-55, wherein at least two doses of said composition are administered.
  • Embodiment 58 The method of any one of embodiments 52-55, wherein two doses of said composition are administered.
  • Embodiment 59 The method of any one of embodiments 52-58, wherein said polypeptide is presented on one or more virus-like particles (VLP).
  • VLP virus-like particles
  • Embodiment 60 The method of embodiment 59, wherein said VLPs are made from viruses selected from the group consisting of Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • Embodiment 61 The method of embodiment 59, wherein said VLPs are made from Q- beta bacteriophage.
  • Embodiment 62 A method for treating a mammal having a coronavirus infection, wherein said method comprises administering to said mammal a composition comprising a polypeptide consisting essentially of or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 1-87 or nucleic acid encoding said polypeptide.
  • Embodiment 63 The method of embodiment 62, wherein said mammal is a human.
  • Embodiment 64 The method of any one of embodiments 62-63, wherein said coronavirus infection is COVID-19.
  • Embodiment 65 The method of any one of embodiments 62-64, wherein said composition comprises an adjuvant or an immunostimulatory molecule.
  • Embodiment 66 The method of embodiment 65, wherein said adjuvant or immunostimulatory molecule is selected from the group consisting of a water in oil emulsion (e.g., Montanide 720, Montanide 51), Complete Freund’s Adjuvant (CFA), Incomplete Freund’s Adjuvant (IF A), a CpG oligonucleotide motif, toll-like receptor 4 (TLR4) agonists (e.g., MiT4, EmT4, A1T4, LiT4), aluminum sulfate, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, monophosphoryl lipid A, aluminumphosphylate, MF59, AS03, AS04, AS03- like, AS04-like, ASOlB-like, GM-CSF, Addavax, AddaS03, retinoic acid-inducible gene I (RIG-I), lipid nanoparticles (e.g., LION), and GLA.
  • Embodiment 67 The method of any one of embodiments 62-66, wherein at least two doses of said composition are administered.
  • Embodiment 68 The method of any one of embodiments 62-66, wherein two doses of said composition are administered.
  • Embodiment 69 The method of any one of embodiments 62-68, wherein said polypeptide is presented on one or more virus-like particles (VLP).
  • VLP virus-like particles
  • Embodiment 70 The method of embodiment 69, wherein said VLPs are made from viruses selected from the group consisting of Parvoviridae, Retro viridae, Flaviviridae, Paramyxoviridae and bacteriophages.
  • Embodiment 71 The method of embodiment 69, wherein said VLPs are made from Q- beta bacteriophage.

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024006362A1 (en) * 2022-06-28 2024-01-04 Transcode Therapeutics, Inc. Nanoparticles and template directed rig-i agonist precursor compositions and uses thereof for cancer therapy

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115947801A (zh) * 2022-12-29 2023-04-11 中国疾病预防控制中心病毒病预防控制所 一种流感病毒通用和冠状病毒联合多肽及其疫苗的应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021214297A1 (en) * 2020-04-23 2021-10-28 Isa Pharmaceuticals B.V. Immunization against sars-cov-related diseases
US11191827B1 (en) * 2020-12-09 2021-12-07 Tevogen Bio Inc. COVID-19 peptide specific T-cells and methods of treating and preventing COVID-19
WO2022023727A1 (en) * 2020-07-28 2022-02-03 Oxford University Innovation Limited Polypeptide panels and uses thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CR20220552A (es) * 2020-04-02 2023-01-17 Regeneron Pharma Anticuerpos contra glicoproteína de espícula anti-sars-cov-2 y fragmentos de unión al antígeno
WO2021204179A1 (en) * 2020-04-09 2021-10-14 Suzhou Abogen Biosciences Co., Ltd. Nucleic acid vaccines for coronavirus

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021214297A1 (en) * 2020-04-23 2021-10-28 Isa Pharmaceuticals B.V. Immunization against sars-cov-related diseases
WO2022023727A1 (en) * 2020-07-28 2022-02-03 Oxford University Innovation Limited Polypeptide panels and uses thereof
US11191827B1 (en) * 2020-12-09 2021-12-07 Tevogen Bio Inc. COVID-19 peptide specific T-cells and methods of treating and preventing COVID-19

Non-Patent Citations (14)

* Cited by examiner, † Cited by third party
Title
ABD ALBAGI SAHAR OBI ET AL: "A multiple peptides vaccine against COVID-19 designed from the nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the immunoinformatics approach", INFORMATICS IN MEDICINE UNLOCKED, vol. 21, 10 November 2020 (2020-11-10), pages 100476, XP055949639, ISSN: 2352-9148, DOI: 10.1016/j.imu.2020.100476 *
BELYAKOV ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 95, 1998, pages 1709 - 1714
CROOKE ET AL., SCI. REP., vol. 10, no. 1, 2020, pages 14179
FOUGEROUX CYRIELLE ET AL: "Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity", NATURE COMMUNICATIONS, vol. 12, no. 1, 12 January 2021 (2021-01-12), XP055938298, Retrieved from the Internet <URL:http://www.nature.com/articles/s41467-020-20251-8> DOI: 10.1038/s41467-020-20251-8 *
GRIFONI ET AL., CELL HOST MICROBE, vol. 27, no. 4, 2020, pages 671 - 680
JACKSON ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 101, 2004, pages 15440 - 15445
LEANA RICH DE MESA HERRERA: "Immunoinformatics approach in designing SARS-CoV-2 vaccine from experimentally determined SARS-CoV T-cell epitopes", JOURNAL OF APPLIED PHARMACEUTICAL SCIENCE, 5 March 2021 (2021-03-05), XP055949634, DOI: 10.7324/JAPS.2021.110303 *
M. WADHWAROBIN THORPE: "Harmonization and standardization of immunogenicity assessment of biotherapeutic products", BIOANALYSIS, vol. 11, no. 17, 2019, pages 1593 - 1604
NELDE ANNIKA ET AL: "SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition", NATURE IMMULOGY, vol. 22, no. 1, 30 September 2020 (2020-09-30), New York, pages 74 - 85, XP055873960, ISSN: 1529-2908, Retrieved from the Internet <URL:https://www.nature.com/articles/s41590-020-00808-x.pdf> DOI: 10.1038/s41590-020-00808-x *
RAMMENSEE HANS-GEORG ET AL: "A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer", JOURNAL FOR IMMUNOTHERAPY OF CANCER, vol. 7, no. 1, 15 November 2019 (2019-11-15), XP055949867, Retrieved from the Internet <URL:http://link.springer.com/article/10.1186/s40425-019-0796-5/fulltext.html> DOI: 10.1186/s40425-019-0796-5 *
RAMMENSEE HANS-GEORG ET AL: "Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups - Supplementary Material", VACCINES, 24 April 2021 (2021-04-24), XP055949877, Retrieved from the Internet <URL:https://www.mdpi.com/2076-393X/9/5/428> [retrieved on 20220808], DOI: 10.3390/vaccines9050428 *
RAMMENSEE HANS-GEORG ET AL: "Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups", VACCINES, vol. 9, no. 5, 24 April 2021 (2021-04-24), pages 428, XP055949127, DOI: 10.3390/vaccines9050428 *
RUCKWARDT ET AL., LANCET RESPIR MED., vol. S2213-2600, no. 21, 2021, pages 00098 - 9
SRIVASTAVA ET AL., BIO,RXIV, 2020.04.01.019299

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024006362A1 (en) * 2022-06-28 2024-01-04 Transcode Therapeutics, Inc. Nanoparticles and template directed rig-i agonist precursor compositions and uses thereof for cancer therapy

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