WO2020160171A1

WO2020160171A1 - Topically formulated antibody compositions for reducing pathogen transmission and methods of using same

Info

Publication number: WO2020160171A1
Application number: PCT/US2020/015713
Authority: WO
Inventors: Sumit Chanda; Tom Wehrman
Original assignee: Sanford Burnham Prebys Medical Discovery Institute
Priority date: 2019-01-29
Filing date: 2020-01-29
Publication date: 2020-08-06

Abstract

Described herein are compositions and methods useful for reducing the likelihood of a pathogenic infection, or for reducing transmission of a pathogen to others, through use of an anti-infective composition that comprises pathogen neutralizing antibodies. The anti-infective compositions disclosed herein are suitable for topical or local application to the surface of an individual's skin or for application to the surface of a solid object.

Description

TOPICALLY FORMULATED ANTIBODY COMPOSITIONS FOR REDUCING PATHOGEN TRANSMISSION AND METHODS OF USING SAME

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No.

62/798,361 filed on January 29, 2019. Priority is claimed pursuant to 35 U.S.C. § 119. The above noted patent application is incorporated by reference as if set forth fully herein.

BACKGROUND OF THE INVENTION

[0002] Pathogenic infections result in substantial morbidity and death worldwide. While vaccination can protect against certain bacterial or viral infections, vaccines are not always fully effective. There are many pathogens for which there is no effective vaccine. Therefore, prevention of infection and transmission of disease are of paramount importance; especially in certain young, elderly, or immunocompromised populations.

SUMMARY OF THE INVENTION

[0003] Disclosed herein, in some embodiments, are anti-infective compositions comprising an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti-infective composition reduces the risk of absorption, infectivity, or transmission of a pathogen. In some embodiments, the neutralizing antibody is specific for a particular pathogen or pathogen subtype. In some embodiments, the neutralizing antibody is a broadly neutralizing antibody (bNAb). In some embodiments, the neutralizing antibody is a monoclonal antibody. In some embodiments, the anti -infective composition comprises a mixture of two or more neutralizing antibodies. In some embodiments, the anti -infective composition is suitable for application to a dermal surface of an individual. In some embodiments, the dermal surface is the individual’s hands, arms, torso, legs, or face. In some embodiments, the anti -infective composition is suitable for application to a solid object. In some embodiments, the solid object is a table, door knob or handle, banister or railing, elevator button, countertop, stovetop, cabinet or cabinet knob or handle, blanket, linen, towel, glove, mask or children’s toy. In some embodiments, the solid object is an examination or surgical glove. In some embodiments, the anti -infective composition is suitable for application to the exterior or interior surface of the examination or surgical glove. In some embodiments, the anti-infective composition further comprises an additional anti -infective agent. In some embodiments, the additional anti -infective active agent is an aminoglycoside, beta-lactam, amphenicol,

fluoroquinolone, fusidic acid, glycopeptide, macrolide, lincosamide, mupirocin, polymixin, sulfonamide, tetracycline, antibacterial antibody, or antibacterial peptide. In some embodiments, the additional anti-infective active agent is conjugated to the neutralizing antibody. In some embodiments, the additional anti-infective agent comprises bacitracin, polymyxin B, or neomycin, or any combinations thereof. In some embodiments, the anti-infective composition is formulated as an aqueous or non-aqueous solution or liquid, spray, aerosol, gel, powder, emulsion, suspension, lotion, cream, ointment, foam, oil, liposome, nanoparticle, paste, or stick. In some embodiments, the anti-infective composition is a soluble aqueous formulation for use in a spray bottle. In some embodiments, the neutralizing antibody neutralizes a respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus, influenza virus, parainfluenza virus, coronavirus, norovirus, rotavirus, hepatitis A virus, adenovirus, astrovirus, S. aureus , methicillin- resistant S. aureus (MRS A), vancomycin-resistant enterococci (VRE), Enterococcus spp ., Enterobacter spp., C. difficile , Campylobacter, E. faecali, E.faecium , or Salmonella.

[0004] Disclosed herein, in some embodiments, are anti-infective compositions comprising an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti -infective composition reduces the risk of absorption, infectivity, or transmission of a pathogen. In some embodiments, the neutralizing antibody neutralizes at least one strain of a group 1 influenza A virus, group 2 influenza A virus, or influenza B virus. In some embodiments, the neutralizing antibody binds an epitope in the influenza virus neuraminidase (NA) protein. In some embodiments, the NA protein is Nl, N2, N3, N4, N5, N6, N7, N8, NO, N10, Ni l, or influenza B NA. In some embodiments, the neutralizing antibody binds an epitope in the influenza virus hemagglutinin (HA) protein. In some embodiments, the HA protein is HI, H2, H3, H4, H5, H6, H7, H8, H9, H10, HI 1, H12, H13, H14, H15, H16, H17, H18, or influenza B HA. In some embodiments, the neutralizing antibody binds an epitope in the globular head domain (HA1) of the influenza virus HA protein. In some embodiments, the neutralizing antibody binds an epitope in the stem domain (HA2) of the influenza virus HA protein. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple strains of the same influenza A subtype. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple influenza A HI strains. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one group 1 influenza A subtype. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one group 2 influenza A subtype. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one influenza B lineage. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 1 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 2 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 1 and group 2 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from both the Yamagata and Victoria influenza B lineages. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from: all group 1 influenza A subtypes, all group 2 influenza A subtypes, both the Yamagata and Victoria influenza B lineages. In some embodiments, the neutralizing antibody binds an epitope in a viral strain of: influenza A H1N1, influenza A H3N2, influenza B Yamagata, or influenza B Victoria, or any combinations thereof. In some embodiments, the anti-infective composition comprises a mixture of three or more neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 1 influenza A viral strain; (b) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 2 influenza A viral strain; and (c) one or more neutralizing antibodies binds an epitope in the HA stem domain of an influenza B

Yamagata lineage or Victoria lineage viral strain. In some embodiments, the anti -infective composition comprises a mixture of two or more neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 1 influenza A viral strain and a Group 2 influenza A viral strain; and (b) one or more neutralizing antibodies binds an epitope in the HA stem domain of an influenza B Yamagata lineage or Victoria lineage viral strain. In some embodiments, the neutralizing antibody is PY102. In some embodiments, the neutralizing antibody is 6F12. In some embodiments, the neutralizing antibody is CR6261 or Cl 79. In some embodiments, the neutralizing antibody is CR8020 or CR8043. In some embodiments, the neutralizing antibody is CR8033 or CR8071. In some embodiments, the neutralizing antibody is F10. In some embodiments, the neutralizing antibody is FI6, a FI6 variant, CR9114, or 81.39.

[0005] Disclosed herein, in some embodiments, are anti-infective compositions comprising an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti -infective composition reduces the risk of absorption, infectivity, or transmission of a pathogen. In some embodiments, the neutralizing antibody neutralizes a respiratory syncytial virus (RSV) subgroup A or subgroup B virus. In some embodiments, the neutralizing antibody binds an epitope in the RSV attachment protein (G) or fusion protein (F). In some embodiments the anti-infective composition comprises a neutralizing antibody that binds an epitope in the RSV F protein, wherein the neutralizing antibody neutralizes both RSV subgroup A and RSV subgroup B viruses. In some embodiments, the neutralizing antibody binds an epitope in antigenic region I, II, IV, or 0 of the RSV F protein. In some embodiments, the neutralizing antibody is 54G10, MAbl9, 1308F, chlOlF, 5C4, D25, MPE8, AM14, AM16, or AM23. In some embodiments, the neutralizing antibody is

palivizumab or motavizumab. In some embodiments, the neutralizing antibody neutralizes a human metapneumovirus (hMPV) subgroup Al, A2, Bl, or B2 virus. In some embodiments, the neutralizing antibody binds an epitope in the hMPV attachment protein (G) or fusion protein (F). In some embodiments, the neutralizing antibody that binds an epitope in the hMPV F protein neutralizes subgroup Al, A2, Bl and B2 hMPV viruses. In some embodiments, the neutralizing antibody binds an epitope in epitope groups 2, 3, 4, 5, and 6 of the hMPV F protein. In some embodiments, the neutralizing antibody is 54G10, DS7, MAb 338, MAb 234, or MAb 628. In some embodiments, the neutralizing antibody binds an epitope in a Pneumovirinae family virus F protein and neutralizes both RSV and hMPV. In some embodiments, the neutralizing antibody is 54G10 or MPE8. In some embodiments, the neutralizing antibody binds an epitope in a norovirus. In some embodiments, the neutralizing antibody binds an epitope in a GII.4 genotype norovirus. In some embodiments, the neutralizing antibody binds an epitope in the major capsid protein of a GII.4 norovirus. In some embodiments, the neutralizing antibody binds an epitope in the P domain of the major capsid protein of a GII.4 norovirus. In some embodiments, the neutralizing antibody binds an epitope in the P2 subdomain of the major capsid protein of a GII.4 norovirus. In some embodiments, the neutralizing antibody is NVB 71.4 or GII.4.2002. G5.

[0006] Disclosed herein, in some embodiments, are anti-allergic compositions comprising an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti-allergic composition reduces the risk of an allergic reaction upon exposure to an allergen or environmental contaminant. In some embodiments, the anti-allergic composition comprises a mixture of two or more neutralizing antibodies. In some embodiments, the anti-allergic composition is suitable for application to a dermal surface of an individual. In some embodiments, the dermal surface is the individual’s hands, arms, torso, legs, or face. In some embodiments, the anti -allergic composition is suitable for application to a solid object. In some embodiments, the anti -allergic composition is applied to an article of clothing. In some embodiments, the anti-allergic composition is formulated as an aqueous or non-aqueous solution or liquid, spray, aerosol, gel, powder, emulsion, suspension, lotions, cream, ointment, foam, oil, liposome, nanoparticle, paste, or stick. In some embodiments, the allergic reaction is caused by a Toxicodendron species of plant. In some embodiments, the neutralizing antibody comprises an anti-urushiol antibody. In some

embodiments, the allergic reaction is caused by an alkylresorcinol. In some embodiments, the allergic reaction is caused by neomycin. In some embodiments, the allergic reaction is caused by an environmental contaminant. In some embodiments, the environmental contaminant is nickel, gold, or chromium.

[0007] Disclosed herein, in some embodiments, are methods of reducing the likelihood of a pathogenic infection comprising, applying an anti-infective composition to a dermal surface, wherein the anti-infective composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, and wherein the anti-infective composition reduces the risk of absorption, transmission, or infectivity of a pathogen.

[0008] Also disclosed herein, in some embodiments, are methods of reducing the transmission of a pathogen comprising, applying an anti -infective composition to a dermal surface, wherein the anti -infective composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, and wherein the anti-infective composition reduces the risk of transmission of a pathogen.

[0009] Further disclosed herein, in some embodiments, are methods of reducing the likelihood of transmission of a pathogenic infection comprising, applying an anti -infective composition to the surface of a solid object, wherein the anti-infective composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient, and wherein the anti-infective composition reduces the risk of fomite driven pathogen transmission.

[0010] In some embodiments, the anti-infective composition is applied to the dermal surface of an individual and reduces the risk of absorption, infectivity, or transmission of the pathogen to the individual. In some embodiments, the anti-infective composition is applied to the dermal surface of an individual and reduces the risk of absorption, infectivity, or transmission of the pathogen to another individual. In some embodiments, the neutralizing antibody is specific for a particular pathogen or pathogen subtype. In some embodiments, the neutralizing antibody is a broadly neutralizing antibody (bNAb). In some embodiments, the neutralizing antibody or bNAb is a monoclonal antibody. In some embodiments, the anti-infective composition comprises a mixture of two or more neutralizing antibodies. In some embodiments, the anti-infective composition is applied to an individual’s hands, arms, torso, legs, or face. In some embodiments, the anti -infective composition further comprises an additional anti-infective agent. In some embodiments, the additional anti -infective active agent is an aminoglycoside, beta-lactam, amphenicol, fluoroquinolone, fusidic acid, glycopeptide, macrolide, lincosamide, mupirocin, polymixin, sulfonamide, tetracycline, antibacterial antibody, or antibacterial peptide. In some embodiments, the additional anti -infective active agent is conjugated to the neutralizing antibody. In some embodiments, the additional anti-infective agent is bacitracin, polymyxin B, or neomycin, or any combinations thereof. In some embodiments, the anti-infective composition is formulated as an aqueous or non-aqueous solution or liquid, spray, aerosol, gel, powder, emulsion, suspension, lotion, cream, ointment, foam, oil, liposome, nanoparticle, paste, or stick. In some embodiments, the anti-infective composition is a soluble aqueous formulation for use in a spray bottle. In some embodiments, the solid object is a table, door knob or handle, banister or railing, elevator button, countertop, stovetop, cabinet or cabinet knob or handle, blanket, linen, towel, glove, mask or children’s toy. In some embodiments, the solid object is an examination or surgical glove. In some embodiments, the anti-infective composition is applied to the exterior or interior surface of the examination or surgical glove. In some embodiments, the anti-infective composition is formulated as a powder, aerosol, spray, gel, emulsion, lotion, cream, or ointment and is applied to the hands or interior surface of the examination or surgical glove. In some embodiments, the pathogenic infection is an infection of respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus, influenza virus, parainfluenza virus, coronavirus, norovirus, rotavirus, hepatitis A virus, adenovirus, astrovirus, S. aureus , methicillin-resistant S. aureus (MRS A), vancomycin-resistant enterococci (VRE), Enterococcus spp ., Enterobacter spp ., C. difficile , Campylobacter, E.faecali, E.faecium , or Salmonella.

[0011] In some embodiments, in the methods disclosed herein, the neutralizing antibody neutralizes at least one strain of a group 1 influenza A virus, group 2 influenza A virus, or influenza B virus. In some embodiments, the neutralizing antibody binds an epitope in the influenza virus neuraminidase (NA) protein. In some embodiments, the NA protein is Nl, N2, N3, N4, N5, N6, N7, N8, NO, N10, Ni l, or influenza B NA. In some embodiments, the neutralizing antibody binds an epitope in the influenza virus hemagglutinin (HA) protein. In some embodiments, the HA protein is HI, H2, H3, H4, H5, H6, H7, H8, H9, H10, HI 1, H12, H13, H14, H15, H16, H17, H18, or influenza B HA. In some embodiments, the neutralizing antibody binds an epitope in the globular head domain (HA1) of the influenza virus HA protein. In some embodiments, the neutralizing antibody binds an epitope in the stem domain (HA2) of the influenza virus HA protein. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple strains of the same influenza A subtype. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple influenza A HI strains. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one group 1 influenza A subtype. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one group 2 influenza A subtype. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one influenza B lineage. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 1 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 2 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 1 and group 2 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from both the Yamagata and Victoria influenza B lineages. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from: all group 1 influenza A subtypes, all group 2 influenza A subtypes, both the Yamagata and Victoria influenza B lineages. In some embodiments, the neutralizing antibody binds an epitope in a viral strain of: influenza A H1N1, influenza A H3N2, influenza B Yamagata, or influenza B Victoria, or any combinations thereof. In some embodiments, the anti-infective composition comprises a mixture of three or more neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 1 influenza A viral strain; (b) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 2 influenza A viral strain; and (c) one or more neutralizing antibodies binds an epitope in the HA stem domain of an influenza B

Yamagata lineage or Victoria lineage viral strain. In some embodiments, the anti-infective composition comprises a mixture of two or more neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 1 influenza A viral strain and Group 2 influenza A viral strain; and (b) one or more neutralizing antibodies binds an epitope in the HA stem domain of an influenza B Yamagata lineage or Victoria lineage viral strain. In some embodiments, the neutralizing antibody is PY102. In some embodiments, the neutralizing antibody is 6F12. In some embodiments, the neutralizing antibody is CR6261 or Cl 79. In some embodiments, the neutralizing antibody is CR8020 or CR8043. In some embodiments, the neutralizing antibody is CR8033 or CR8071. In some embodiments, the neutralizing antibody is F10. In some embodiments, the neutralizing antibody is FI6, a FI6 variant, CR9114, or 81.39. [0012] In some embodiments, in the methods disclosed herein, the neutralizing antibody neutralizes a respiratory syncytial virus (RSV) subgroup A or subgroup B virus. In some embodiments, the neutralizing antibody binds an epitope in the RSV attachment protein (G) or fusion protein (F). In some embodiments, the neutralizing antibody binds an epitope in the RSV F protein, wherein the neutralizing antibody neutralizes both RSV subgroup A and RSV subgroup B viruses. In some embodiments, the neutralizing antibody binds an epitope in antigenic region I, II, IV, or 0 of the RSV F protein. In some embodiments, the neutralizing antibody is 54G10, MAbl9, 1308F, chlOlF, 5C4, D25, MPE8, AM14, AM16, or AM23. In some embodiments, the neutralizing antibody is palivizumab or motavizumab. In some embodiments, the neutralizing antibody neutralizes a human metapneumovirus (hMPV) subgroup Al, A2, Bl, or B2 virus. In some embodiments, the neutralizing antibody binds an epitope in the hMPV attachment protein (G) or fusion protein (F). In some embodiments, the neutralizing antibody that binds an epitope in the hMPV F protein neutralizes subgroup Al, A2, Bl and B2 hMPV viruses. In some embodiments, the neutralizing antibody binds an epitope in epitope groups 2, 3, 4, 5, and 6 of the hMPV F protein. In some embodiments, the neutralizing antibody is 54G10, DS7, MAb 338, MAb 234, or MAb 628. In some embodiments, the neutralizing antibody binds an epitope in a Pneumovirinae family virus F protein and neutralizes both RSV and hMPV. In some embodiments, the neutralizing antibody is 54G10 or MPE8. In some embodiments, the neutralizing antibody binds an epitope in a GII.4 genotype norovirus. In some embodiments, the neutralizing antibody binds an epitope in the major capsid protein of a GII.4 norovirus. In some embodiments, the neutralizing antibody binds an epitope in the P domain of the major capsid protein of a GII.4 norovirus. In some embodiments, the neutralizing antibody binds an epitope in the P2 subdomain of the major capsid protein of a GII.4 norovirus. In some embodiments, the neutralizing antibody is NVB 71.4 or GII.4.2002. G5.

[0013] Disclosed herein, in some embodiments, are methods of reducing the likelihood or severity of an allergic reaction in an individual comprising: applying an anti -allergic composition to the surface of the individual’s skin, wherein the anti -allergic composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti -allergic composition reduces the risk of an allergic reaction upon exposure to an allergen or environmental contaminant. Also disclosed herein, in some embodiments, are methods of reducing the likelihood or severity of an allergic reaction in an individual comprising: applying an anti-allergic composition to the surface of a solid object, wherein the anti-allergic composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or suitable excipient, wherein the anti-allergic composition reduces the risk of an allergic reaction upon exposure to an allergen or environmental contaminant. In some embodiments, the anti-allergic composition comprises a mixture of two or more neutralizing antibodies. In some embodiments, the anti-allergic composition is applied to the individual’s hands, arms, legs, feet, torso, or face. In some embodiments, the anti-allergic composition is applied to an article of clothing. In some embodiments, the anti-infective composition is formulated as an aqueous or non-aqueous solution or liquid, spray, aerosol, gel, powder, emulsion, suspension, lotions, cream, ointment, foam, oil, liposome, nanoparticle, paste, or stick. In some embodiments, the allergic reaction is caused by a Toxicodendron species of plant. In some embodiments, the allergic reaction is caused by an alkylresorcinol. In some embodiments, the allergic reaction is caused by neomycin. In some embodiments, the allergic reaction is caused by an environmental contaminant. In some embodiments, the environmental contaminant is nickel, gold, or chromium. In some

embodiments, the anti-allergic composition comprises an anti-urushiol antibody.

INCORPORATION BY REFERENCE

[0014] All publications, patents, and patent applications mentioned in this specification are incorporated by reference herein to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative

embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0016] FIG. 1 exemplifies a representative viral plaque assay of PR8 influenza A virus treated with neutralizing antibodies PY102 and 6F12. Prior to viral neutralization, PY102 and 6F12 were incubated at room temperature for a period of up to 14 days.

[0017] FIG. 2 exemplifies the number of viral plaques observed in the plaque assay of FIG. 1. No plaques were observed in either the negative control or the 0-day or 14-day PY102 or 6F12 neutralizing antibody incubated samples. In contrast, a large number of viral plaques were observed in the virus only positive control sample.

[0018] FIG. 3 depicts human norovirus blockade antibody response sera from a goat before and after immunization against multivalent virus-like particles (VLPs). Multivalent

immunization resulted in generation of blockade antibodies to all four components of the vaccine: GI.3 DSV, GI.4 Chiba, GII.4 2012 Sydney and GII.2 SMV. Serum collected pre immunization (“pre-bleed”) did not block VLP binding at the lowest dilution tested.

[0019] FIG. 3A depicts IC50 of blockade antibodies against GI.3 DSV (“GI.3”).

[0020] FIG. 3B depicts IC50 of blockade antibodies against GI.4 Chiba (“GI.4”).

[0021] FIG. 3C depicts IC50 of blockade antibodies against GII.4 2012 Sydney (“GII.4 2012”).

[0022] FIG. 3D depicts IC50 of blockade antibodies against GII.2 SMV (“GII.2”).

[0023] FIG. 4 depicts human norovirus blockade antibody response sera from a second goat before and after immunization against multivalent virus-like particles (VLPs). Multivalent immunization resulted in generation of blockade antibodies to all four components of the vaccine: GI.3 DSV, GI.4 Chiba, GII.4 2012 Sydney and GII.2 SMV. Serum collected pre immunization (“pre-bleed”) did not block VLP binding at the lowest dilution tested.

[0024] FIG. 4A depicts IC50 of blockade antibodies against GI.3 DSV (“GI.3”).

[0025] FIG. 4B depicts IC50 of blockade antibodies against GI.4 Chiba (“GI.4”).

[0026] FIG. 4C depicts IC50 of blockade antibodies against GII.4 2012 Sydney (“GII.4 2012”).

[0027] FIG. 4D depicts IC50 of blockade antibodies against GII.2 SMV (“GII.2”).

[0028] FIG. 5 depicts human norovirus blockade antibody response sera from a third goat before and after immunization against multivalent virus-like particles (VLPs). Multivalent immunization resulted in generation of blockade antibodies to all four components of the vaccine: GI.3 DSV, GI.4 Chiba, GII.4 2012 Sydney and GII.2 SMV. Serum collected pre immunization (“pre-bleed”) did not block VLP binding at the lowest dilution tested.

[0029] FIG. 5A depicts IC50 of blockade antibodies against GI.3 DSV (“GI.3”).

[0030] FIG. 5B depicts IC50 of blockade antibodies against GI.4 Chiba (“GI.4”).

[0031] FIG. 5C depicts IC50 of blockade antibodies against GII.4 2012 Sydney (“GII.4 2012”).

[0032] FIG. 5D depicts IC50 of blockade antibodies against GII.2 SMV (“GII.2”).

[0033] FIG. 6 illustrates the human norovirus blockade antibody response in bleed 4 sera from the three goats shown in FIG. 3-5 individually and pooled together. The sera block binding of all four vaccine VLP components as well as the non-immunizing GII.4 2009 VLP.

[0034] FIG. 6A depicts IC50 of blockade antibodies against GI.3 DSV (“GI.3”).

[0035] FIG. 6B depicts IC50 of blockade antibodies against GI.4 Chiba (“GI.4”).

[0036] FIG. 6C depicts IC50 of blockade antibodies against GII.4 2012 Sydney (“GII.4 2012”).

[0037] FIG. 6D depicts IC50 of blockade antibodies against GII.2 SMV (“GII.2”).

[0038] FIG. 6E depicts IC50 of blockade antibodies against GII.4 2009 VLP (“GII.4 2009”).

[0039] FIG. 7 shows the potency of IgG purified from the pooled human norovirus VLP hyper-immunized goat serum in FIG. 6 against the four immunizing VLPs. VLP binding was measured with IgG before and after gamma irradiation, with and without inclusion of the lotion base. IgG, both before and after irradiation and with or without the lotion base, blocked VLP binding. Lotion alone interfered with VLP -ligand binding; however the lotion and the antibody did not have a cumulative or opposing effect on the blockade of VLP binding.

[0040] FIG. 7A depicts IC50 of blockade antibodies against GI.3 DSV.

[0041] FIG. 7B depicts IC₅₀ of blockade antibodies against GI.4 Chiba.

[0042] FIG. 7C depicts IC50 of blockade antibodies against GII.4 2012 Sydney (“GII.4 2012”).

[0043] FIG. 7D depicts IC50 of blockade antibodies against GII.2 SMV.

[0044] FIG. 8 shows the potency of IgG purified from the pooled human norovirus VLP hyper-immunized goat serum in FIG. 6 against four VLPs not included in the immunization.

VLP binding was measured with IgG before and after gamma irradiation, with and without inclusion of the lotion base. Blockade antibody potency did not extend to VLPs of genotypes I and II not included in the immunization. At high concentrations purified IgG did display cross blockade functionality against VLPs from genogroup GII.4.

[0045] FIG. 8A depicts IC50 of blockade antibodies against GI.l NV.

[0046] FIG. 8B depicts IC₅₀ of blockade antibodies against GII.4 2002.

[0047] FIG. 8C depicts IC₅₀ of blockade antibodies against GII.4 2006b.

[0048] FIG. 8D depicts IC₅₀ of blockade antibodies against GII.4 2009.

[0049] FIG. 9 illustrates blockade of human norovirus VLP binding to ligand by an antibody- containing lotion (“AvLo”). AvLo contains irradiated IgG purified from serum collected from goats following multivalent immunization. AvLo blocks ligand binding of VLPs included in the multivalent immunization (GII.4 2012 Sydney, GII.2 SMV, GI.3 DSV and GI.4 Chiba) as well as select non-immunized GII.4 VLPs (GII.4 2006b. P3.D301, GII.4 2009 New Orleans and GII.4 2015 Sydney).

[0050] FIG. 9A depicts IC₅₀ of blockade antibodies against immunizing VLPs.

[0051] FIG. 9B depicts IC₅₀ of blockade antibodies against non-immunizing VLPs and GII.4

Sydney.

DETAILED DESCRIPTION OF THE INVENTION

[0052] The role of antibodies in host protection against viral infections is well established.

Antibodies typically neutralize viral infection by targeting the surface exposed viral

glycoproteins (lipid-enveloped viruses) or capsid shells (non-enveloped viruses). A distinctive property of antigenic viral glycoproteins and capsid shells are their capacity to vary the antigenic surface while maintaining function, a property endowing viruses with the capacity to escape antibody neutralization and vaccine response. Accordingly, neutralizing antibodies directed to conserved regions of a viral antigen are ideal, not only for their ability to remain effective in the face of antigenic change, but for their capacity to potentially neutralize viruses across multiple strains, species, or genera.

[0053] Disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual or reducing transmission of a pathogen to other individuals comprising applying an anti-infective composition to the surface of the individual’s skin, wherein the anti-infective composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, and wherein the anti -infective composition reduces the risk of absorption, transmission, or function of a pathogen in the individual or transmission of a pathogen to another individual.

[0054] Also disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual comprising applying an anti -infective composition to the surface of a solid object, wherein the anti -infective composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient, wherein the anti -infective composition reduces the risk of fomite driven pathogen transmission.

[0055] In some embodiments, the anti-infective composition is in a topical formulation. In some embodiments, the anti -infective composition is in a formulation suitable for application to a solid object. Exemplary formulations include, but are not limited to aqueous or non-aqueous solutions or liquids, sprays, aerosols, gels, powders, emulsions, suspensions, lotions, creams, ointments, foams, oils, liposomes, nanoparticles, pastes, or sticks. Formulations of the anti- infective compositions described herein can be directly applied, preferably to the surface of the skin, by any appropriate method, such as by aerosol, spray bottle, droplet bottle, squeeze bottle, moisturized cotton ball or pad, suitable applicators such as wipes or strips, or by the hands or fingers.

[0056] In some embodiments, the anti-infective composition is applied to the hands to reduce the likelihood of contracting or transmitting a pathogenic infection. In some embodiments, the anti-infective composition is applied to the forearms, face, or any other surface of the skin (excluding the mucous membranes) that could come into contact with virus-contaminated respiratory droplets or particles.

[0057] In some embodiments, the anti-infective composition is applied to the surface of a solid object to reduce the likelihood of fomite driven pathogen transmission. In some embodiments, the anti -infective compositions described herein are applied to the surface of any suitable object that could come into contact with virus-contaminated respiratory droplets, particles, or contaminated individuals. In some embodiments, the anti-infective composition is applied to the surface of objects that are frequently handled or touched by an individual’s hands. Exemplary solid objects include, but are not limited to: tables, door knobs or handles, banisters or railings, elevator buttons, countertops, stovetops, cabinets and cabinet knobs and handles, blankets, linens, towels, and children’s toys. In some embodiments, the solid object is an examination or surgical glove. In some embodiments, the anti -infective composition is applied to the exterior or interior surface of the examination or surgical glove. In some embodiments, the anti-infective

composition is formulated as a powder, aerosol, spray, gel, emulsion, lotion, cream, or ointment, and is applied to the hands or interior surface of the examination or surgical glove. In some embodiments, the anti-infective composition is applied to a surgical mask.

[0058] Other embodiments of the methods disclosed herein comprise application of the anti- infective composition to the surface of a solid object located in, but not limited to: a hospital, medical professional’s office, nursing home convalescent home, skilled nursing facility, or place of residence for people who require continual nursing care, as well as any other facility, community, or residence where pathogens are more concentrated or individuals are more susceptible to infection ( e.g ., the young, elderly, or immunocompromised).

Certain Terminology

[0059] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the claimed subject matter belongs. It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed. In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that, as used in the specification and the appended claims, the singular forms“a,”“an,” and“the” include plural referents unless the context clearly dictates otherwise. Furthermore, use of the term“including” as well as other forms, such as“include,” “includes,” and“included,” is not intended to be limited solely to the recited items. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0060] The term“topical administration” or“topical application” in accordance with the present invention relates to an application or administration of the disclosed anti-infective composition that is applied body surfaces, such as the surface of the skin, to reduce the likelihood of acquiring or transmitting a pathogenic infection. The term“topical administration” or “topical application,” as it is used herein, is not meant to encompass the mucus membranes (e.g., intranasal) or ophthalmic use (e.g, onto the conjunctiva). As a route of administration, topical administration or application is contrasted with enteral ( e.g ., in the gastrointestinal tract) and parenteral (e.g., intramuscular or intravenous injection) administration or application. In its broadest sense, a topical administration or application may be understood, from a

pharmacological perspective, as having a local, non-systemic effect.

[0061] The term“neutralizing antibody,” as used herein, generally refers to an antibody or antibody conjugate complex that can bind to an epitope on a pathogen thereby neutralizing a biological effect of the pathogen. A neutralizing biological effect includes, but is not limited to, reducing the likelihood of a pathogen being absorbed by a host, binding a receptor on a host cell, fusing with or otherwise gaining entry inside of a host cell, or being transmitted form one host or object to another host or object.

[0062] The term“broadly neutralizing antibody” (“bNAb”), as used herein, generally refers to a neutralizing antibody that exhibits neutralizing activity against multiple strains, species, or genera of a pathogen.

[0063] The terms“effective amount” or“therapeutically effective amount,” as used herein, generally refer to a sufficient amount of an agent or a compound (e.g, the anti-infective composition described herein) which will relieve, to some extent, or reduce the likelihood of the occurrence of one or more of the symptoms of the disease or condition being treated. The result can be reduction and/or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. The terms“effective amount” or“therapeutically effective amount” typically include, for example, a prophylactically effective amount. For example, a“prophylactically effective amount” is the amount of the topically formulated anti- infective composition described herein that is required to reduce the risk of absorption, transmission, or function of a pathogen in an individual or transmission of a pathogen to another individual.

[0064] The terms“about” or“approximately,” as used herein, generally mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part upon how the value is measured or determined, i.e., the limitations of the measurement system. For example,“about” can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively,“about” can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, within 5-fold, and more preferably within 2-fold of a value. Antibodies

[0065] As used herein, the term“antibody” generally refers to an immunoglobulin (Ig) molecule that specifically binds to, or is immunologically reactive toward, a specific antigen. Antibodies include, but are not limited to, polyclonal antibodies, monoclonal antibodies, genetically engineered antibodies, epitope binding fragments of antibodies, and antibody-derived polypeptides ( e.g ., single chain variable fragments and single domain antibodies).

[0066] Conventional antibodies are glycoproteins produced by plasma cells in response to a foreign molecule (immunogen). Conventional antibodies typically exhibit the same basic tetrameric structure consisting of two heavy chains and two light chains paired to form two (divalent) identical antigen binding Fab arms attached by a flexible hinge region to the stem of the antibody, the Fc region. In mammals, there are five heavy chain (H) isotypes (a, d, e, g, and m) and two light chain (L) isotypes (K and l). The heavy chain isotype determines the overall class of an antibody (IgA, IgD, IgE, IgG, or IgM respectively), which primarily differ in the effector functions elicited upon antigen binding. In some embodiments, the neutralizing antibodies disclosed herein are of the IgG class. IgG is the most abundant serum antibody and provides the majority of antibody-based immunity against invading pathogens. IgG consists of four human subclasses (IgGl, IgG2, IgG3, and IgG4) and five murine subclasses (IgGl, IgG2a, IgG2b, IgG2c, and IgG3). Because subclass nomenclature has arisen independently for each species, there is no general relationship between the subclasses from each species. For a given species, the IgG subclasses are highly homologous and differ mainly in the hinge region and the extent to which they activate the host immune system.

[0067] Each IgG heavy chain comprises a heavy chain variable region (V_H) and a heavy chain constant region (C_H) containing 3 domains (C_HI , C_H2 and C_H3). Each IgG light chain comprises a light chain variable region (V_L) and a light chain constant region (C_L). Together, the variable region (V_H and V_L) of each heavy/light chain pair forms the antigen binding sites of an antibody. However, in some embodiments, only the heavy chain variable domain is required. For example, naturally occurring camelid antibodies contain only a heavy chain and are functional and stable in the absence of a light chain (see, e.g., Muyldermans, Annu. Rev. Biochem., 2013, 82:775-97). The V_H and V_L regions each contain three epitope binding hypervariable loops (called

complementary determining regions (CDRs)), which are interspersed by four relatively conservative framework regions (FRs) that position and align the CDRs in three-dimensional space.

[0068] The basic unit of a conventional or“complete” antibody is a four polypeptide immunoglobulin protein containing two heavy chains and two light chains held together via disulfide bonds and include a complete Fc region. In the methods disclosed herein, unless otherwise specified, the term“antibody” includes not only a“complete” antibody, but also epitope binding fragments (also known as antigen binding fragments) of that antibody, as well as other genetically engineered, epitope binding antibodies and antibody-derived polypeptides.

[0069] As used herein, an epitope binding fragment of an antibody is generally defined as a portion of a complete antibody capable of binding the same epitope as the complete antibody, albeit not necessarily to the same extent. Although several types of epitope binding fragments are possible, in some embodiments, the epitope binding fragment comprises at least one pair of heavy and light chain variable regions (VH and VL, respectively) held together (e.g, by disulfide bonds) to preserve the antigen binding site. In other embodiments, the epitope binding fragments described herein do not contain a functional Fc region (i.e., do not stimulate effector functions, e.g. , activation of the classical complement pathway or stimulation of antibody-dependent cellular cytotoxicity (ADCC)). Epitope binding fragments of an antibody are obtained from a given antibody using any suitable technique known by those skilled in the art (e.g, recombinant DNA technology, or enzymatic or chemical cleavage of a complete antibody), and are typically screened for specificity in the same manner in which complete antibodies are screened. In some embodiments, an epitope binding fragment comprises an F(ab’)₂ fragment, Fab’ fragment, Fab fragment, Fd fragment, or Fv fragment. In some embodiments, the term“antibody” includes antibody-derived polypeptides, such as single chain variable fragments (scFv), diabodies or other multimeric scFvs, heavy chain antibodies, single domain antibodies, or other polypeptides comprising a sufficient portion of an antibody (e.g, one or more CDR regions) to confer specific antigen binding ability to the polypeptide.

[0070] In some embodiments, the neutralizing antibody comprises an F(ab’)₂ fragment. An F(ab’)₂ fragment contains the two antigen-binding regions (divalent) joined together through disulfide bonds and is void of most, but not all, of the Fc region. The F(ab’)₂ fragment comprises the VL, CL, VH, and CHI domains and can be generated, for example, by pepsin digestion of a complete antibody. In some embodiments, the neutralizing antibody comprises an Fab’ fragment. An Fab’ fragment comprises the VL, CL, VH, and CHI domains and can be formed, for example, by reduction of the F(ab’)₂ fragment hinge region disulfide bonds to yield two monovalent antigen binding Fab’ fragments. In some embodiments, the neutralizing antibody comprises an Fab fragment. An Fab fragment contains a single antigen-binding region

(monovalent) and is void of most, but not all, of the Fc region. The Fab fragment comprises the VL, CL, VH, and CHI domains and can be produced, for example, by papain digestion of a complete antibody to yield two Fab fragments. In some embodiments, the neutralizing antibody comprises an Fd fragment. An Fd fragment (monovalent) comprises the heavy chain V_H and C_H I domain and can be produced, for example, by reduction of the interchain disulfide bonds of a Fab or Fab’ fragment. In some embodiments, the neutralizing antibody comprises an Fv fragment.

An Fv fragment (monovalent) comprises the light and heavy chain variable domains (V_L and V_H), and can be generated, for example, by pepsin digestion of a Fab’ fragment. The V_H and V_L chains of an Fv fragment can be held together by non-covalent interactions, or can be crosslinked with, e.g ., glutaraldehyde, disulfide bonds, or a peptide linker. The antibodies and epitope binding fragments described herein include antibodies and epitope binding fragments that are produced by modification of complete antibodies (e.g, enzymatic cleavage) or those synthesized de novo using recombinant DNA technology.

[0071] In some embodiments, the neutralizing antibody comprises a single chain variable fragment. A single chain variable fragment (scFv) is a genetically engineered Fv-type fragment containing the V_H and V_L domains joined together by a flexible linker into a single polypeptide chain. Suitable peptide linkers include repeated amino acid sequences (e.g., (GGGGS)_nor (GS)_n) and are typically 15-20 amino acids in length. While scFvs are typically monovalent monomers, they can be engineered to be multimeric, bivalent, and/or bispecific molecules (e.g, a single peptide chain with two V_H and two V_L regions, yielding tandem scFvs that can recognize two different epitopes; see also Holliger, et al, Proc. Natl. Acad. Sci. USA, Jul 1993; 90(14): 6444- 6448 for a description and production of bivalent, bispecific dimers of scFvs known as “diabodies”).

[0072] In some embodiments, the neutralizing antibody comprises a heavy chain antibody. A heavy chain antibody is an IgG antibody comprising two heavy chain polypeptides, but lacking the light chain polypeptides present in conventional antibodies. For example, naturally occurring camelid (e.g, camel or llama) antibodies contain only a heavy chain, but are fully functional and stable in the absence of a light chain. Similarly, cartilaginous fishes (e.g, sharks) produce a homodimeric heavy chain antibody referred to as“immunoglobulin new antigen receptor” (IgNAR) composed of only a homodimeric heavy chain which contains one variable and five constant domains for each chain.

[0073] In some embodiments, the neutralizing antibody comprises a single domain antibody.

A single domain antibody is an antibody fragment comprising a single monomeric variable antibody domain (typically from the heavy chain) that is able to selectively bind to a specific antigen. Recombinant antigen-specific, single domain antibodies engineered from the variable region (VHH) of camelid heavy-chain antibodies are known as nanobodies (Ablynx NV).

Through the use of peptide linkers, a single nanobody can be engineered as a multi- specific, multivalent, and/or bi-paratopic (binding multiple identical or different epitopes on the same target) antibody-derived molecule (see, e.g ., Muyldermans, Annu. Rev. Biochem., 2013, 82:775-97). Similar to camelid-derived VHH nanobodies, recombinant antigen-specific, single domain antibodies engineered from the variable region (VNAR) of cartilaginous fish heavy-chain antibodies (IgNARs) display high stability under conditions that would otherwise compromise the integrity of traditional monoclonal antibodies.

[0074] In some embodiments, the neutralizing antibody is a multi-specific antibody (i.e., binds multiple epitopes). As used herein, the term“antibody” includes not only conventional, monospecific (i.e., binds a single epitope) antibody molecules, but also recombinant, bispecific (i.e., binds two different epitopes on the same or different antigen) engineered antibodies and their epitope binding fragments. See Kontermann, el al, Drug Discov. Today, Jul 2015, 20(7):838-47 for a review of bispecific antibody technology.

[0075] In some embodiments, the neutralizing antibody is a human antibody. In some embodiments, the neutralizing antibody is a non-human antibody (e.g, a mouse monoclonal antibody). In some embodiments, the neutralizing antibody is“humanized.” As used herein, the term“humanized” antibody generally refers to an engineered antibody (or epitope binding fragment thereof) which contains sequences derived from a human antibody and sequences derived from a non-human antibody. Typically, humanized antibodies comprise at least one (and typically two) non-human variable regions (V_H and V_L) in which all, or substantially all, of the CDR regions correspond to a non-human antibody (e.g, mouse, rat or rabbit) and in which all, or substantially all, of the FR regions correspond to a human antibody. In some instances, some FR amino acids of a humanized antibody may be replaced by the corresponding amino acids of a non-human antibody to further improve or optimize the properties of the antibody. In other embodiments, the humanized antibody comprises at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin consensus sequence.

[0076] In some embodiments, the neutralizing antibody is a“chimeric” antibody. As used herein, the term“chimeric antibody” refers to an antibody wherein part of the light and/or heavy chain is derived from one antibody (e.g, a specific species or antibody class or subclass), while the other part of the light chain and/or heavy chain is derived from another antibody (which may be from an identical or different species or belong to an identical or different antibody class or subclass), provided that the antibody still retains the desired antigen binding activity. In some embodiments, a chimeric antibody is made by genetically engineering the V_H and V_L domains from one species (e.g, a mouse) with the Fc region from another species, such as a human. [0077] In some embodiments, an antibody is further modified using any suitable technique known in the art, for example, by including an amino acid deletion, insertion, substitution, or any other modification ( e.g ., posttranslational and chemical modifications, such as glycosylation or phosphorylation), either alone or in combination. In some instances, the modification further comprises a modification for modulating antibody interaction with Fc receptors. Any suitable method known to those skilled in the art can be utilized for introducing such modifications, e.g., by modifying the nucleic acid sequence underlying the amino acid sequence of an antibody. Neutralizing Antibodies

[0078] Disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual or reducing transmission of a pathogen to other individuals comprising applying an anti-infective composition to the surface of the individual’s skin, wherein the anti-infective composition comprises a neutralizing antibody and a

pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti- infective composition reduces the risk of absorption, transmission, or function of a pathogen in the individual or transmission of a pathogen to another individual. Also disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual comprising applying an anti -infective composition to the surface of a solid object, wherein the anti-infective composition comprises a neutralizing antibody and a pharmaceutically acceptable carrier or excipient, wherein the anti-infective composition reduces the risk of fomite driven pathogen transmission.

[0079] In some embodiments, the pathogen includes, but is not limited to, respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus, influenza virus, parainfluenza virus, coronavirus, norovirus, rotavirus, metapneumovirus (MPV), hepatitis A virus, adenovirus, astrovirus, S. aureus, methicillin-resistant S. aureus (MRS A), vancomycin-resistant enterococci (VRE), Enterococcus spp., Enterobacter spp., C. difficile, Campylobacter, E. faecali, E.faecium, or Salmonella.

[0080] In some embodiments, a non-neutralizing antibody is engineered to be a neutralizing antibody. For example, in some instances, an antibody will bind an antigen on a pathogen, but this interaction itself is not sufficient to neutralize the pathogen ( i.e ., the antibody is a“non neutralizing antibody”). However, in some embodiments, conjugation of a non-neutralizing antibody to another chemical moiety or compound results in the neutralization of a pathogen {i.e., the antibody conjugate is a“neutralizing antibody”) by, e.g. , preventing the adsorption of the pathogen. [0081] In some embodiments, the neutralizing antibody comprises an antibody, or an epitope binding fragment thereof, conjugated to another chemical moiety. In some embodiments, the neutralizing antibody comprises an antibody conjugated to another chemical moiety, wherein the neutralizing antibody conjugate prevents the adsorption or transmission of a pathogen. In some embodiments, the neutralizing antibody comprises an antibody conjugated to another chemical moiety, wherein the conjugated moiety renders the neutralizing antibody conjugate larger than the antibody alone, thereby preventing absorption or transmission of the pathogen. In some embodiments, the neutralizing antibody comprises an antibody conjugated to another chemical moiety, wherein the conjugated moiety renders the neutralizing antibody conjugate more hydrophilic than the antibody alone, thereby preventing absorption or transmission of the pathogen. In some embodiments, the neutralizing antibody comprises an antibody conjugated to another chemical moiety, wherein the conjugated moiety renders the neutralizing antibody conjugate more hydrophobic than the antibody alone, thereby preventing absorption or transmission of the pathogen. In some embodiments, the neutralizing antibody comprises an antibody conjugated to another chemical moiety, wherein the conjugated moiety binds a polypeptide on a pathogen. In some embodiments, the neutralizing antibody comprises an antibody conjugated to another chemical moiety, wherein the conjugated moiety binds a polypeptide on an individual. In some embodiments, the neutralizing antibody comprises an antibody conjugated to a polypeptide. In some embodiments, the neutralizing antibody comprises an antibody conjugated to a targeting agent. In some embodiments, the neutralizing antibody comprises an antibody conjugated to another antibody or epitope binding fragment of another antibody. In some embodiments, the neutralizing antibody comprises an antibody conjugated to a lipid moiety. In some embodiments, the neutralizing antibody comprises an antibody conjugated to a drug. Various methods of antibody conjugation are available and any suitable method of conjugation is contemplated by the disclosure herein.

Influenza

[0082] Each year, worldwide influenza epidemics result in substantial morbidity and death, with the young and elderly representing the majority of this mortality. Influenza is transmitted through direct contact with infected individuals, by contact with influenza-contaminated objects, and through inhalation of virus-laden, aerosolized respiratory droplets. Vaccination is currently the most effective method to prevent infection, but influenza vaccines must be reformulated annually due to antigenic variation in the immunogenic glycoprotein hemagglutinin (HA).

Furthermore, a particular influenza vaccine usually confers protection for no more than a few years and typically does not include all the strains active in the world during a given flu season. Moreover, the influenza vaccine may not be particularly effective in older individuals and those with weaker immune systems, who often have a lower protective immune response after flu vaccination compared to younger and/or healthier individuals.

[0083] Influenza virus is a lipid-enveloped, single-stranded negative-sense RNA virus that contains eight segmented genomic fragments that each encodes either one or two proteins. A total of four segments encode the non- structural viral replicative proteins while the remaining segments encode the influenza structural proteins. A lipid bilayer surrounds a matrix protein structural core, which compartmentalizes the nucleoprotein bound RNA genome. Influenza contains two membrane-embedded, surface protruding glycoproteins that function as viral antigens: hemagglutinin (HA), which is responsible for binding to sialic-acid receptors and entry into host cells, and neuraminidase (NA), which is involved in budding of new virions from infected cells.

[0084] There are four phylogenetically and antigenically distinct genera of influenza virus (A- D), with influenza viruses A-C able to infect human populations. While influenza A and B are responsible for seasonal epidemics of disease, influenza type C generally causes only mild respiratory illness and does not contribute to epidemic disease. Influenza A exhibits the greatest genetic diversity of all the influenza genera and causes the vast majority of severe disease in humans. There are numerous antigenically distinct subtypes of influenza A, which are classified according to the HA and NA surface glycoproteins. There are currently 18 HA and 11 NA subtypes (HI through HI 8 and N1 through N11 respectively), but influenza viruses are constantly changing. For example, small genetic variations in the influenza genome accumulate over time as the virus replicates (“antigenic drift”). While these mutations usually produce viruses that share similar antigenic properties, occasionally selective pressure over time results in antigenically distinct influenza viruses and the need for vaccine reformulation.

[0085] Because of its segmented genome and ability to infect multiple hosts (aquatic birds serve as the natural reservoir for all influenza A viruses), influenza A can undergo major, abrupt reassortments of its genetic material (“antigenic shift”) to result in novel HA and/or NA antigen combinations that cause pandemic human infection. Such emergent strains are typically so antigenically distinct from the same subtype in humans, that most individuals have no immunity to the novel virus. For example, the 2009 H1N1 pandemic strain is a reassortment of avian, human, and swine influenza viruses.

[0086] Influenza B viruses are not divided into subtypes, but can be further broken down into lineages and strains. Currently circulating influenza B viruses typically belong to one of two lineages: Yamagata and Victoria. Influenza B virus can cause disease symptoms similar to influenza A, and in some years is probably responsible for more illness than influenza A.

Although there have been examples of influenza B and C viruses transmitting to other hosts, they are essentially human viruses and do not have a natural reservoir from which they can recruit antigenically novel surface antigens like influenza.

[0087] Antibodies that neutralize influenza infectivity are primarily directed against the surface glycoproteins, in particular the HA protein. The influenza HA protein is composed of two major domains: the immunodominant globular head (HA1) domain, in which the majority of antigenic variation occurs, and the stem/stalk (HA2) domain, which remains relatively conserved between influenza virus strains. The globular HA head mediates binding to cell surface sialic acid, while the HA stem mediates fusion between the viral and host cellular membranes. The eighteen subtypes of HA share between 40% and 60% amino acid homology and cluster into two major phylogenetic groups: group 1 (comprising HI, H2, H5, H6, H8, H9, Hi t, H12, H13, H16, H17, and H18) and group 2 (comprising H3, H4, H7, H10, H14, and H15). While the globular head is the major target of neutralizing antibodies that inhibit virus binding to target cells, such antibodies typically do not cross-react across a broad range of influenza strains. In contrast, because the HA stem is far more conserved among viral strains and less tolerant of mutation, anti-HA stem neutralizing antibodies tend to neutralize across a broad selection of influenza viral strains. Besides their differences in breadth of reactivity, anti-globular head antibodies are generally more potent than anti-stem neutralizing antibodies. Nevertheless, antigenic drift in the HA1 domain can drive viral escape mutants thereby reducing the effectiveness of HA anti -head neutralizing antibodies.

[0088] Disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual or reducing transmission of a pathogen to other individuals comprising applying an anti-infective composition to the surface of the individual’s skin, wherein the anti-infective composition comprises a neutralizing antibody and a

pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti- infective composition reduces the risk of absorption, transmission, or function of a pathogen in the individual or transmission of a pathogen to another individual. Also disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual comprising applying an anti -infective composition to the surface of a solid object, wherein the anti-infective composition comprises a neutralizing antibody and a pharmaceutically acceptable carrier or excipient, wherein the anti-infective composition reduces the risk of fomite driven pathogen transmission. [0089] In some embodiments, the pathogen is an influenza virus. In some embodiments, the neutralizing antibody binds an epitope in the influenza NA protein. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein globular head domain. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein stem domain. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple strains of the same influenza A subtype ( e.g ., multiple HI strains). In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one group 1 influenza A subtype. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one group 2 influenza A subtypes. In some

embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from more than one influenza B lineage. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 1 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 2 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all group 1 and group 2 influenza A subtypes. In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all circulating influenza B lineages (e.g., Yamagata and Victoria lineages). In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from all influenza A subtypes and all circulating influenza B lineages.

[0090] In some embodiments, the neutralizing antibody binds an epitope in the influenza virus subtypes H1N1, H3N2, influenza B Yamagata lineage, influenza B Victoria lineage, or any combinations thereof. In some embodiments, the anti-infective composition comprises a mixture of neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 1 influenza A viral strain; (b) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 2 influenza A viral strain; and (c) one or more neutralizing antibodies binds an epitope in the HA stem domain of an influenza B Yamagata lineage or Victoria lineage viral strain. In some embodiments, the anti-infective composition comprises a mixture of two or more neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in the HA stem domain of a Group 1 and Group 2 influenza A viral strain; (b) one or more neutralizing antibodies binds an epitope in the HA stem domain of an influenza B Yamagata lineage or Victoria lineage viral strain.

[0091] In some embodiments, the neutralizing antibody binds an epitope in the influenza A HA protein stem domain, wherein the antibody can neutralize multiple strains of epidemic HI viruses. An exemplary antibody that can neutralize a broad selection of epidemic HI viruses is mouse monoclonal antibody 6F12, or an epitope binding fragment thereof (see Tan, et al ., J. Virol. Jun 2012, 86(11):6179-88 for a description and characterization of 6F12 as well as exemplary methods to produce similar antibodies). In some embodiments, the neutralizing antibody is a chimeric or humanized derivative of 6F12 (see, e.g ., Shembeker, et al., Biotech. J., Dec 2014, 9(12): 1594-603 for exemplary methods of humanization of a mouse H1N1 neutralizing antibody).

[0092] In some embodiments, the neutralizing antibody binds an epitope in the influenza A HA protein stem domain, wherein the antibody can neutralize at least HI, H5, and H9 influenza A viruses. An exemplary antibody that can neutralize at least influenza A HI, H5, and H9 is human monoclonal antibody CR6261 (see Throsby, et al, PLoS ONE, 2008, 3(12):e3942;

Ekiert, et al. , Science. Apr 2009, 324(5924):246-251; GenBank Accession Nos.: HI919031 and HI919031; and U.S. Pat. App. Pub. 20090311265 for a description and characterization of CR6261 as well as exemplary methods to produce similar antibodies). Another exemplary antibody that can neutralize at least HI, H5, and H9 influenza A is mouse monoclonal antibody C179 (Takara Bio USA, Inc., Catalog #: M145), or an antigen binding fragment thereof (see Okuno, et al. , J. Virol., May 1993, 67(5):2552-8; Sakabe, et al, Antiviral Res., Dec

2010;88(3):249-55; and U.S. Pat. App. Pub. 20020054882 for a description and characterization of Cl 79 as well as exemplary methods to produce similar antibodies). In some embodiments, the neutralizing antibody is a chimeric or humanized derivative of Cl 79.

[0093] In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein stem domain and cross-reacts with at least H3 and H7 group 2 influenza A subtypes. Exemplary antibodies that can neutralize at least influenza A H3 and H7 are human monoclonal antibodies CR8020 and CR8043 (see Ekiert, et al, Science, Aug 2011, 333(6044):843-850 and GenBank Accession Nos.: JN093123.1 and JN093122.1 for a description and characterization of CR8020; see Friesen, et al, Proc. Natl. Acad. Sci., Jan 2014, 111(1):445— 450; GenBank Accession Nos.: LP724599.1 and LP724597.1; and U.S. Pat. App. Pub. 20160304586 for a description and characterization of CR8043 as well as exemplary methods to produce similar antibodies). [0094] In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein and cross-reacts with all influenza B subtypes. Exemplary influenza B neutralizing antibodies include human monoclonal antibodies CR8033 and CR8071 (see Dreyfus, et al ., Science, Sep 2012, 337(6100): 1343-1348; and GenBank Accession Nos.: JX213636.1 and JX213635.1 for a description and characterization of CR8033 and CR8071 as well as exemplary methods to produce and analyze similar antibodies).

[0095] In some embodiments, the anti-infective composition comprises a mixture of two or more neutralizing antibodies. In some embodiments, the anti-infective composition comprises a mixture of (a) one or more neutralizing antibodies that neutralize two or more group 1 influenza A viruses and (b) one or more neutralizing antibodies that neutralize two or more group 2 influenza A viruses. In some embodiments, the anti-infective composition comprises a mixture of (a) one or more neutralizing antibodies that neutralize at least HI, H5, and H9 influenza A viruses and (b) one or more neutralizing antibodies that neutralize at least H3 and H7 influenza A viruses. In some embodiments, (a) the neutralizing antibody that neutralizes at least HI, H5, and H9 influenza A viruses comprises human monoclonal antibody CR6261 and (b) the neutralizing antibody that neutralizes at least H3 and H7 influenza A viruses comprises human monoclonal antibody CR8020.

[0096] In some embodiments, the anti-infective composition comprises a mixture of (a) one or more neutralizing antibodies that neutralize a viral strain from two or more group 1 influenza A viruses; (b) one or more neutralizing antibodies that neutralize a viral strain from two or more group 2 influenza A viruses; and (c) one or more neutralizing antibodies that neutralize a viral strain from two or more influenza B virus lineages. In some embodiments, the anti -infective composition comprises a mixture of (a) one or more neutralizing antibodies that neutralize a viral strain from at least HI, H5, and H9 influenza A viruses; (b) one or more neutralizing antibodies that neutralize a viral strain from at least H3 and H7 influenza A viruses; and (c) one or more neutralizing antibodies that neutralize a viral strain from at least the Yamagata and Victoria influenza B virus lineages. In some embodiments, (a) the neutralizing antibody that neutralizes a viral strain from at least HI, H5, and H9 influenza A viruses comprises human monoclonal antibody CR6261; (b) the neutralizing antibody that neutralizes a viral strain from at least H3 and H7 influenza A viruses comprises human monoclonal antibody CR8020; and (c) the neutralizing antibody that neutralizes a viral strain from at least the Yamagata and Victoria influenza B viruses comprises human monoclonal antibody CR8033 or CR8071.

[0097] In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein stem domain and neutralizes a viral strain from all group 1 influenza A subtypes. An exemplary neutralizing antibody is F10 (see Sui, et al. , Nat Struct. Mol. Biol., Mar 2009, 16(3):265-273 and U.S. Pat. App. Pub. 20120128684 for a description and characterization of F10 as well as exemplary methods to produce and analyze similar antibodies).

[0098] In some embodiments, the neutralizing antibody binds an epitope in the influenza HA protein stem domain and cross-reacts with all group 1 and group 2 influenza A subtypes. An exemplary group 1 and group 2 neutralizing antibody is human monoclonal antibody FI6 (see Corti, et al ., Science. Sep 2012, 337(6100): 1343-48; GenBank Accession Nos.: JN234430- JN234448; and U.S. Pat. App. Pub. 20110274702 for a description and characterization of FI6 and FI6 variants, as well as exemplary methods to produce and analyze similar antibodies).

Other exemplary group 1 and group 2 neutralizing antibodies include human monoclonal antibody 81.39a (see Marjuki, et al, J. Virol., Nov. 2016, 90(23): 10446-10458 for a description and characterization of hMAb 81.39a) and human monoclonal antibody CR9114 (see Dreyfus, et al. , Science, Sep 2012, 337(6100): 1343-1348; and GenBank Accession Nos.: JX213640.1 and JX213639.1 for a description and characterization of CR9114, which is also effective against influenza B viruses, as well as exemplary methods to produce and analyze similar antibodies).

[0099] Other exemplary neutralizing antibodies that can be utilized in the methods disclosed herein include mouse monoclonal antibody 9H10 (neutralizes at least H3 and H10 influenza A viruses, see Tan, et al ., J. Virol., Dec 2014, 88(23):13580-92 for a description and

characterization of MAb 9H10 as well as exemplary methods to produce and analyze similar antibodies); human monoclonal antibodies 39.29 and 81.39 (neutralizes at least HI, H2, and H3 influenza A viruses, see Nakamura, et al. , Cell Host Microbe, Jul 2013, 14(1):93-103 for a description and characterization of MAb 39.29 and Mab 81.39 as well as exemplary methods to produce and analyze similar antibodies); human monoclonal antibody C05 (neutralizes at least at least HI, H2, H3, and H9, see Ekiert, et al. , Nature. 2012 Sep 27; 489(7417): 526-532; and GenBank Accession Nos.: JX206997.1 and JX206996.1 for a description and characterization of MAb C05 as well as exemplary methods to produce and analyze similar antibodies); human monoclonal antibody A05 (neutralizes at least HI and H5, see Kashyap, et al. , Proc Natl Acad Sci USA, Apr 2008, 105(16): 5986-5991 and Kashyap, et al. , PLoS Pathog., Jul 2010,

6(7):el000990 for a description and characterization of MAb A05 as well as exemplary methods to produce and analyze similar antibodies).

[0100] See also U.S. Pat. App. Pubs. 20130289246; 20160176953; 20150037352;

20120058124; 20140046039; 20160264648; and 20130302348 for a description and

characterization of other exemplary neutralizing monoclonal antibodies and exemplary methods to produce and analyze similar antibodies. Respiratory Syncytial Virus (RSV)

[0101] Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in infants and young children worldwide. Although most infants hospitalized for RSV infection are previously healthy and have no known risk factors, certain populations are at high risk of developing serious lower respiratory tract disease caused by RSV. Those at high risk include infants with: prematurity, chronic lung disease, congenital heart disease, pulmonary abnormalities, neuromuscular disease, immunodeficiency, Down syndrome, cystic fibrosis, or children in regions where the burden of RSV disease is significantly greater than the general US population. Hospitalized children, elderly adults, immunocompromised adults, transplant patients, asthmatic individuals, or those with cardiopulmonary disease are also at high risk of developing complications from severe RSV infection. RSV is typically transmitted through direct contact with virus-containing respiratory droplets, such as those generated through sneezing or coughing, or by indirect contact with RSV-contaminated fomites, such as used tissues or doorknobs. There is no current vaccine for RSV and prevention is the best defense against infection for the majority of the population. For children at high risk of serious RSV infection, hospitalizations can be reduced through monthly injections with the FDA-approved monoclonal antibody palivizumab.

[0102] RSV is an enveloped, single-stranded negative-sense RNA virus that encodes a total of 11 proteins. Two of these proteins are replicative, nonstructural proteins while the remaining eight are structural proteins. A lipid bilayer surrounds a matrix protein structural core, which compartmentalizes the nucleoprotein bound RNA genome. RSV contains three membrane- embedded, surface protruding glycoproteins; the small hydrophobic protein (SH), the attachment protein (G), and the fusion protein (F).

[0103] RSV is subdivided into A and B subgroups based upon the amino acid sequence of the G and F proteins. While the G protein amino acid sequences displays a wide variance between the A and B subgroups (-30% identity), the F protein is typically more conserved (-90% identity). Because of their role in viral attachment and fusion, the surface exposed G and F glycoproteins are the major proteins involved in RSV infection and antibodies directed against either the G or F protein have been shown to neutralize virus infectivity. However, F protein is likely the preferred antigenic target of protective immunity as only the highly conserved F protein elicits a high serum neutralizing antibody response that is cross-reactive with both RSV subgroups.

[0104] The RSV F fusion protein contains a number of known neutralizing antibody antigenic regions, including antigenic sites I-IV (antigenic sites II and IV are also known as sites A and C respectively). For example, palivizumab is a humanized monoclonal antibody directed against an epitope RSV F protein antigenic site A/P. See Arbiza, et al. , J. Gen. Virol., Sept 1992, 73:2225-2234; Lopez, et al. , J. Virol. Aug 1998, 72(8):6922-6928; McLellan, et al., J. Virol., Dec. 2010, 12236-12244; and McLellan, Curr. Opin. Virol., Apr 2015, 11 :70-75 for

characterization of and exemplary methods to determine RSV antigenic sites.

[0105] Disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual or reducing transmission of a pathogen to other individuals comprising applying an anti-infective composition to the surface of the individual’s skin, wherein the anti-infective composition comprises a neutralizing antibody and a

pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti- infective composition reduces the risk of absorption, transmission, or function of a pathogen in the individual or transmission of a pathogen to another individual. Also disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual comprising applying an anti -infective composition to the surface of a solid object, wherein the anti-infective composition comprises a neutralizing antibody and a pharmaceutically acceptable carrier or excipient, wherein the anti-infective composition reduces RSV subgroup A or subgroup B virus. In some embodiments, the neutralizing antibody binds an epitope in the RSV F or G protein. In some embodiments, the neutralizing antibody binds an epitope in the RSV F protein, wherein the neutralizing antibody cross reacts with both A and B RSV

subgroups. In some embodiments, the neutralizing antibody binds an epitope in antigenic region I, II, IV, or 0 of the RSV F protein. Antigenic region IV is sometimes referred to as antigenic regions IV- VI.

[0106] In some embodiments, the neutralizing antibody binds an epitope in antigenic site II of the RSV F glycoprotein. Exemplary antigenic site II neutralizing antibodies include 47F, AK13A2, 7C2, B4, B5, 11, and/or 13 (see Arbiza, et al., J. Gen. Virol., Sept 1992, 73:2225- 2234; and Lopez, et al., J. Virol. Aug 1998, 72(8):6922-6928 for a description and

characterization of these antibodies). Additional exemplary antigenic site II neutralizing antibodies include monoclonal antibodies 1436C, 1153, 1142, 151, 1200, 1214, 1237, 1129, and/or 1121 (see, e.g ., Beeler, et al, J Virol. Jul 1989, 63(7):2941-50 for a description and characterization of these antibodies). In some embodiments, the neutralizing antibody is an epitope binding fragment of any of the aforementioned antigenic site II neutralizing antibodies.

In some embodiments, the neutralizing antibody is a chimeric or humanized version of any the aforementioned antigenic site II neutralizing antibodies (see, e.g. , U.S. Pat. App. Pub.

20090104205 for a description of humanized MAb 1129 and exemplary methods to produce similar humanized antibodies from mouse monoclonal antibody CDRs). In some embodiments, the neutralizing antibody is palivizumab, or an antigen binding fragment thereof. In some embodiments, the neutralizing antibody is a palivizumab-derivative antibody that demonstrates improved binding affinity for RSV F-protein compared to palivizumab (see Wu, et al ., J. Mol. Biol., 2005, 350:126-144 for examples of modified palivizumab antibodies with improved binding kinetics and neutralization efficacy and exemplary methods for generating optimized and/or improved anti-F protein neutralizing antibodies). In some embodiments, the palivizumab- derivative neutralizing antibody is motavizumab (MEDI-524).

[0107] In some embodiments, the neutralizing antibody binds an epitope in antigenic site IV of the RSV F glycoprotein. Exemplary antigenic site IV neutralizing antibodies include monoclonal antibodies 52F, 56F, 57F, MAbl9 (19), MAb20 (20), 7.957, 7.936, 8.858, 8.075, 8.138, 8.139, 7.916, and/or 9.432 (see Arbiza, et al, J. Gen. Virol., Sept 1992, 73:2225-2234; and Lopez, et al ., J. Virol. Aug 1998, 72(8):6922-6928 for a description and characterization of these antibodies). Additional exemplary antigenic site IV neutralizing antibodies include 1243,

1331H, 1308F, and/or 1302A (see, e.g., Beeler, et al, J. Virol., Jul 1989, 63(7):2941-50 for a description and characterization of these antibodies). In some embodiments, the neutralizing antibody is an epitope binding fragment of the aforementioned antigenic site IV neutralizing antibodies. In some embodiments, the neutralizing antibody is a chimeric or humanized version of the aforementioned antigenic site IV neutralizing antibodies (see, e.g., U.S. Pat. App. Pub. 20090104205 for a description of humanized antibody 1308F and exemplary methods to produce similar humanized antibodies from mouse monoclonal antibody CDRs). In some embodiments, the neutralizing antibody is humanized MAbl9 (RSHZ19/Felvizumab). In some embodiments, the neutralizing antibody is mouse monoclonal antibody 10 IF, or an epitope binding fragment thereof. In some embodiments, the neutralizing antibody is a 101F chimeric antibody (chlOlF), or an epitope binding fragment thereof (see Wu, et al, J. Gen. Virol., 2007 88: 2719-272; and U.S. Pat. App. Pub. 20060159695 for a description and characterization of lOlF/chlOlF and exemplary methods to generate and antibodies and determine residues critical for antibody binding). In some embodiments, the neutralizing antibody is an affinity matured derivative of chlOlF.

[0108] In some embodiments, the neutralizing antibody binds an epitope in antigenic site 0 of the RSV F glycoprotein (see, e.g., Kwakkenbos, et al, Nat. Med. Jan 2010, 16(1): 123-128, McLellan, et al, Science, May 2013, 340(6136): 1113-1117 for a description and

characterization of antigenic site 0). Exemplary antigenic site 0 neutralizing antibodies includes mouse monoclonal antibody 5C4 and human monoclonal antibodies D25 and AM22 (see, McLellan, et al., Science, May 2013, 340(6136): 1113-1117 for a description and characterization of antigenic site 0 and antibody 5C4; Kwakkenbos, et al ., Nat. Med., Jan 2010, 16(1): 123-128 and U.S. Pat. App. Pub. 20100239593 for a description and characterization of D25; and U.S. Pat. App. Pub. 20120070446 for a description and characterization of AM22). In some embodiments, the neutralizing antibody is MEDI8897 (a D25 variant). In some

embodiments, the neutralizing antibody is a chimeric or humanized version of a mouse monoclonal antigenic site 0 neutralizing antibody (see, e.g ., U.S. Pat. App. Pub. 20160031972 for a description of humanized antibody 5C4 and exemplary methods to produce similar mouse and humanized monoclonal antibodies). Additional exemplary antigenic site 0 neutralizing antibodies include human antibodies AM14, AM16, and AM23 (see Kwakkenbos, et al ., Nat. Med., Jan 2010, 16(1): 123-128 and U.S. Pat. App. Pub. 20100239593 for a description and characterization of these antibodies).

[0109] In some embodiments, the neutralizing antibody is human monoclonal antibody RSD5, RSE13, RSB27 or RSB28; or an epitope binding fragment thereof (see Corti, et al. , Nature, Sept 2013, 501(7467):439-43 for a description and characterization of these antibodies and exemplary methods for producing and analyzing similar antibodies).

[0110] In some embodiments, the neutralizing antibody binds an epitope in the antiparallel b2/b7 strands of the RSV F protein (see, e.g., Corti, et al. , Nature, Sept 2013, 501(7467):439-43). In some embodiments, the neutralizing antibody binds an epitope in the antiparallel b2/b7 strands of the RSV F protein and comprises amino acid residues T50, D305, G307, 1309 or D310. In some embodiments, the neutralizing antibody binds an epitope in the antiparallel b2/b7 strands of a Pneumovirinae family F protein and comprises the cognate amino acid residues of RSV F protein residues T50, D305, G307, 1309 or D310. In some embodiments, the neutralizing antibody binds an epitope in the antiparallel b2/b7 strands of the RSV F protein and is human monoclonal antibody MPE8. In some embodiments, the neutralizing antibody binds an epitope in the antiparallel b2/b7 strands of the Pneumovirinae family F protein and is human monoclonal antibody MPE8. See Corti, et al ., Nature, Sept 2013, 501(7467):439-43 and U.S. Pat. App. Pub. 20160046675 for a description and characterization of MPE8 and exemplary methods for producing and analyzing similar antibodies.

[0111] See, e.g, U.S. Pat. App. Pub. 20140377279 for methods of generating, characterizing, and testing of human RSV neutralizing antibodies.

Human metapneumovirus (hMPV)

[0112] Human metapneumovirus (hMPV) is a pathogenic respiratory virus in the

Pneumovirinae family that is genetically related to RSV and causes respiratory tract illnesses ranging from a mild cough to bronchiolitis and pneumonia. Like RSV, hMPV is an enveloped, single- stranded negative-sense RNA virus that expresses both the attachment glycoprotein (G) and the fusion glycoprotein (F).

[0113] hMPV isolates are divided into four subgroups (Al, A2, Bl, and B2) based upon the amino acid sequence of the G and F proteins. Because of the high level of sequence conservation of the F protein across all hMPV subgroups (-94%), this protein is the preferred antigenic target for the generation of cross-subgroup neutralizing antibodies. The hMPV F fusion protein contains a number of known neutralizing antibody antigenic regions, including epitope groups 2, 3, 4, 5, and 6. See, e.g ., Ulbrandt, et al., J. Gen. Virol., 2008, 89:3113-3118 for characterization of hMPV epitope groups and exemplary methods to determine hMPV antigenic sites. The hMPV F protein epitope group 4 corresponds to the cognate antigenic site II/A site defined for the RSV F protein that is recognized by the neutralizing anti-RSV antibody palivizumab.

[0114] Disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual or reducing transmission of a pathogen to other individuals comprising applying an anti-infective composition to the surface of the individual’s skin, wherein the anti-infective composition comprises a neutralizing antibody and a

[0115] In some embodiments, the pathogen is hMPV. In some embodiments, the neutralizing antibody binds an epitope in the hMPV F or G protein. In some embodiments, the neutralizing antibody binds an epitope in the hMPV F protein, wherein the neutralizing antibody cross reacts with Al, A2, Bl, and B2 hMPV subgroups. In some embodiments, the neutralizing antibody binds an epitope in epitope group 2, 3, 4, 5, or 6 of the RSV F protein.

[0116] In some embodiments, the neutralizing antibody binds an epitope in epitope group 4 of the hMPV F glycoprotein. Exemplary epitope group 4 neutralizing antibodies include MAb 338, MAb 234, and MAb 628 (see Ulbrandt, et al., J Virol., Aug 2006, 80(16):7799-80 for a description and characterization of MAb 338, MAb 234, and MAb 628 and exemplary methods for producing and analyzing similar antibodies). In some embodiments, the neutralizing antibody is an epitope binding fragment of the aforementioned hMPV epitope group 4 neutralizing antibodies. In some embodiments, the neutralizing antibody is a chimeric or humanized version of the aforementioned hMPV epitope group 4 neutralizing antibodies.

[0117] In some embodiments, the neutralizing antibody binds an epitope in epitope group 5-6 of the hMPV F glycoprotein. In some embodiments, the neutralizing antibody is human monoclonal antibody 54G10 (see Schuster, et al. , J. Infect. Dis., Jan 2015, 211(2):216-25 for a description and characterization of 54G10 and exemplary methods for producing and analyzing similar antibodies)

[0118] In some embodiments, the neutralizing antibody is DS7 (see Williams, et al ., J. Virol. Aug 2007; 81(15):8315-24 for a description and characterization of DS7 and for an example of an antibody that binds an epitope in the hMPV F protein and exemplary methods to produce and screen hMPV F protein neutralizing antibodies). Any neutralizing antibody directed against the RSV or hMPV F protein, or any improvements or optimization of those antibodies, is

contemplated by the present disclosure (see, e.g ., Wu, et al., J. Mol. Biol., 2005, 350: 126-144 for exemplary methods for generating optimized and/or improved anti-F protein antibodies).

Norovirus

[0119] Norovirus (NoV) is the leading cause of severe acute viral gastroenteritis. Although the severity of disease is usually moderate, infection can be especially virulent in young children, the elderly, and the immunocompromised. There is no vaccine or treatment for norovirus, and prevention is the best defense against this virus.

[0120] NoV is classified into five genogroups (GI to GV), each including a number of different genotypic subgroups. Although GI, GII, and GIV NoVs can all infect humans, GII.4 subgroup strains cause the vast majority of norovirus outbreaks worldwide. Norovirus disease patterns typically include epidemic outbreaks of disease every 2-3 years, whereby the predominant circulating GII.4 strain is replaced by a new antigenically distinct GII.4 strain. For example, strain US95/96 (GII.4.1997) caused the pandemic that occurred during the mid-1990s. This was followed by the emergence of the Farmington Hills strain (GII.4.2002) in 2002, the Hunter strain (GII.4.2004) in 2004, the Minerva strain (GII.4.2006) in 2006, the New Orleans strain

(GII.4.2009) in 2009, and the Sydney strain (GII.4.2012) in 2012. This pattern of GII.4 strain replacement over time correlates with antigenic differences between the circulating strain and the emergent strain, suggesting that the emergence of new GII.4 strains is driven by pressure to escape human herd immunity.

[0121] Norovirus is a non-enveloped, single-stranded positive-sense RNA virus that encodes three open reading frames (ORFs). ORFl encodes a non-structural polyprotein, while ORF2 and ORF3 encode the major and minor capsid proteins, respectively. The major capsid monomer is structurally divided into a shell domain (S), which forms the core of the particle, and a protruding domain (P) that extends away from the core. The P domain is further divided into the PI and P2 subdomains. The P2 subdomain is the most exposed region of the viral particle, binds to host histo-blood group antigens (HBGAs), and contains the major antigenic sites targeted by NoV neutralizing antibodies. Coinciding with these functions, changes in the P2 amino acid sequence of GII.4 strains occur frequently and correlate with the emergence of new epidemic strains with altered carbohydrate ligand binding and antigenicity profiles.

[0122] Disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual or reducing transmission of a pathogen to other individuals comprising applying an anti-infective composition to the surface of the individual’s skin, wherein the anti-infective composition comprises a neutralizing antibody and a

[0123] In some embodiments, the pathogen is norovirus. In some embodiments, the neutralizing antibody binds an epitope in a GI or GII norovirus. In some embodiments, the neutralizing antibody binds an epitope in a GII.4 norovirus. In some embodiments, the neutralizing antibody binds an epitope in a GII.4 NoV major capsid protein. In some

embodiments, the neutralizing antibody binds an epitope in the P domain of the GII.4 NoV major capsid protein. In some embodiments, the neutralizing antibody binds an epitope in the P2 subdomain of the GII.4 NoV major capsid protein (see, e.g ., Lindesmith, et al ., J. Virol., Jan 2012, 86(2):873-83; Lindesmith, et al., PLoS Pathog., 2012, 8(5):el002705; Lindesmith, et al ., J. Virol., Mar 2013, 87(5):2803-13; Debbink, et al. , J. Infect. Dis., 2013, 208(11): 1877-1887;

Lindesmith, et al. , J. Virol., Aug 2014, 88(16):8826-42; and U.S. Pat. App. Pub. 20140271712 for exemplary GII.4 P2 domain antigenic regions, GII.4 neutralizing antibodies, and methods for the design, selection, and characterization of NoV neutralizing antibodies).

[0124] In some embodiments, the neutralizing antibody is GII.4.2006. G2, GII.4.2006. G3,

GII.4.2006. G4, GII.4.2006.G5, GII.4.2006.G6, GII.4.2006.G7, or any combinations thereof (see Lindesmith, et al, J. Virol., Mar 2013, 87(5):2803-13 for a description and characterization of exemplary monoclonal antibodies). In some embodiments, the neutralizing antibody is an epitope binding fragment of GII.4.2006.G2, GII.4.2006.G3, GII.4.2006.G4, GII.4.2006.G5, GII.4.2006.G6, GII.4.2006.G7, or any combinations thereof. In some embodiments, the neutralizing antibody is GII.4.2002.G5, or an epitope binding fragment thereof (see Lindesmith, et al. , J. Virol., Aug 2014, 88(16):8826-42 for a description and characterization of

GII.4.2002.G5 - commercially available as MBS227P from Maine Biotechnology Services, Inc). In some embodiments, the aforementioned mouse monoclonal antibodies are recombinant, humanized, and/or chimeric. In another embodiment, the neutralizing antibody is NVB 71.4 (a broadly neutralizing human GII.4 monoclonal antibody isolated from a healthy blood donor, see Debbink, et al ., J. Infect. Dis., 2013, 208(11): 1877-1887 and Lindesmith, et al ., J. Virol., Aug 2014, 88(16):8826-42 for a description and characterization of NVB 71.4 and other exemplary human monoclonal antibodies).

[0125] Because of GII.4 antigenic variation over time, the neutralizing antibody may need to be reformulated over time. Tracking sequence and antigenic changes of newly emergent NoV strains to reveal new patterns of viral evolution should allow identification of new blockade epitopes for neutralizing antibody design and production. See Lindesmith, et al ., PLoS Pathog. 2012;8(5):el002705; Lindesmith, et al. , J. Virol., Mar 2013, 87(5):2803-13; Debbink, et al, J. Infect. Dis., 2013, 208(11): 1877-1887; and Lindesmith, et al. , J. Virol. Aug 2014, 88(16):8826- 42 for exemplary methods used to characterize evolving antigenic regions in newly emergent GII.4 noroviruses for the design and selection of neutralizing antibodies specifically tailored to new pandemic norovirus strains.

Allergens and Environmental Contaminants

[0126] Disclosed herein, in some embodiments, are methods of reducing the likelihood or severity of an allergic reaction in an individual, the methods comprising applying an anti-allergic composition to the surface of the individual’s skin, wherein the anti-allergic composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti -allergic composition reduces the risk of an allergic reaction upon exposure to an allergen or environmental contaminant. Also disclosed herein, in some embodiments, are methods of reducing the likelihood or severity of an allergic reaction in an individual, the methods comprising applying an anti-allergic composition to the surface of a solid object, wherein the anti -allergic composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient, wherein the anti-allergic composition reduces the risk of an allergic reaction upon exposure to an allergen or environmental contaminant.

[0127] In some embodiments, the allergic reaction is caused by a Toxicodendron species of plant. In some embodiments, the allergic reaction is caused by an alkylresorcinol. In some embodiments, the allergic reaction is caused by neomycin. In some embodiments, the allergic reaction is caused by an environmental contaminant. In some embodiments, the environmental contaminant is nickel, gold, or chromium. In some embodiments, the anti-allergic composition is applied to the individual’s hands, arms, legs, torso, or face. In some embodiments, the solid object is an article of the individual’s clothing. In some embodiments, the anti-allergic composition comprises an anti-urushiol antibody. In some embodiments, the anti-allergic composition comprises an anti-urushiol antibody and the anti-allergic composition is formulated as a gel, emulsion, lotion, cream, or ointment.

Combination Therapies

[0128] Disclosed herein, in some embodiments, are methods useful for reducing the likelihood of a pathogenic infection in an individual or reducing transmission of a pathogen to other individuals comprising applying an anti-infective composition to the surface of the individual’s skin, wherein the anti-infective composition comprises a neutralizing antibody and a

[0129] In some embodiments, the anti-infective composition further comprises an additional anti-infective agent. In some embodiments, the additional anti-infective agent is an

aminoglycoside, beta-lactam, amphenicol, fluoroquinolone, fusidic acid, glycopeptide, macrolide, lincosamide, mupirocin, polymixin, sulfonamide, tetracycline, antibacterial antibody, or antibacterial peptide. Exemplary antibiotics include, but are not limited to: polymyxin B sulfate /bacitracin zinc, polymyxin B/neomycin, polymyxin B/neomycin/gramicidin, polymyxin B/trimethoprim, polymyxin B/bacitracin, neomycin, ciprofloxacin, moxifloxacin, ofloxacin, gatifloxacin, levofloxacin, tobramycin, azithromycin, gentamicin, erythromycin, and bacitracin. [0130] In some embodiments, the anti-infective active agent is conjugated to the neutralizing antibody. Antibody conjugation techniques are well known in the art and any suitable method of conjugation is contemplated herein.

Formulations

[0131] Disclosed herein, are methods useful for reducing the likelihood of a pathogenic infection in an individual or reducing transmission of a pathogen to other individuals comprising applying an anti-infective composition to the surface of the individual’s skin, wherein the anti- infective composition comprises a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti -infective composition reduces the risk of absorption, transmission, or function of a pathogen in the individual or transmission of a pathogen to another individual. Also disclosed herein, are methods useful for reducing the likelihood of a pathogenic infection in an individual comprising applying an anti- infective composition to the surface of a solid object, wherein the anti -infective composition comprises a neutralizing antibody and a pharmaceutically acceptable carrier or excipient, wherein the anti-infective composition reduces the risk of fomite driven pathogen transmission.

[0132] In some embodiments, the anti-infective composition is formulated in a formulation suitable for local administration. In some embodiments, the anti-infective composition is formulated in a formulation suitable for application to a solid object. In some embodiments, the anti-infective composition is formulated in a formulation suitable for topical application. Topical formulations or formulations suitable for application to a solid object include, but are not limited to: aqueous or non-aqueous solutions or liquids, sprays, aerosols, gels, powders, emulsions, suspensions, lotions, creams, ointments, foams, oils, liposomes, nanoparticles, pastes, or sticks. Those skilled in the art will appreciate that a wide variety of cosmetically, dermatologically, or pharmaceutically acceptable carriers and excipients carriers may be employed according to the present invention. Any disclosure surrounding topical formulations of the anti-infective compositions discussed herein are equally applicable to formulations suitable for application to a solid object.

Liquids

[0133] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of an aqueous solution or liquid. In some embodiments, the topical formulation comprises an aqueous solution of the anti -infective composition and a pharmaceutically acceptable carrier or excipient. Any carrier and/or excipient suitable for topical application is contemplated by the disclosure herein and described in more detail below. In some embodiments, pharmaceutically acceptable carriers or excipients disclosed herein include, but are not limited to, one or more: pH modifying agent ( e.g ., buffering agents), stabilizing agents, thickening agents, colorant agents, preservative agents, emulsifying agents, solubilizing agents, antioxidant agents, or any combination thereof.

[0134] In some embodiments, the topical formulation comprises an aqueous solution of the anti-infective composition and a pharmaceutically acceptable carrier or excipient, wherein the aqueous solution is in the form of a spray, mist, or aerosol. In some embodiments, the aqueous solution of the anti -infective composition and a pharmaceutically acceptable carrier or excipient is formulated as a gel, paste, powder, emulsion, suspension, lotion, cream, ointment, foam, oil, liposome, nanoparticle, or stick.

[0135] Formulations of the anti -infective compositions described herein can be directly applied, preferably to the surface of the skin or solid object, by any appropriate method, such as by aerosol, spray bottle, droplet bottle, squeeze bottle, moisturized cotton ball or pad, suitable applicators such as wipes or strips, or by the hands or fingers. In some embodiments, the anti- infective composition is placed into an appropriate dispenser such as a spray bottle, squeeze bottle, jar, tube, capsule or vial. In some embodiments, the anti-infective composition is pressurized or comprises a gaseous propellant or other aerosolizing agent.

Gels

[0136] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of a gel. In some embodiments, gels are semisolid (or semi-rigid) systems consisting of dispersions of large organic molecules dispersed in a liquid that is rendered semisolid by the action of a thickening agent or polymeric material dissolved or suspended in the liquid vehicle. In some embodiments, gels are water- soluble and are removed using warm water or saline.

[0137] Gels include a single-phase or a two-phase system. A single-phase gel consists of organic macromolecules distributed uniformly throughout a liquid in such a manner that no apparent boundaries exist between the dispersed macromolecules and the liquid. Some single phase gels are prepared from synthetic macromolecules (e.g., carbomer) or from natural gums (e.g, tragacanth). In some embodiments, single-phase gels are generally aqueous, but can also be made using alcohols and oils. Two-phase gels consist of a network of small discrete particles.

[0138] Gels can also be classified as being hydrophobic or hydrophilic. In some embodiments, the base of a hydrophobic gel comprises liquid paraffin with polyethylene or fatty oils gelled with colloidal silica, or aluminum or zinc soaps. In contrast, the base of hydrophilic gels usually comprises water, glycerol, or propylene glycol gelled with a suitable gelling agent (e.g, tragacanth, starch, cellulose derivatives, carboxyvinylpolymers, and magnesium-aluminum silicates). Other suitable gelling agents include, but are not limited to: modified celluloses, such as hydroxypropyl cellulose and hydroxyethyl cellulose; Carbopol homopolymers and

copolymers; and combinations thereof. Suitable solvents in the liquid vehicle include, but are not limited to: diglycol monoethyl ether; alklene glycols, such as propylene glycol; dimethyl isosorbide; alcohols, such as isopropyl alcohol and ethanol. Other additives, which improve the skin feel and/or emolliency of the formulation, may also be incorporated. Examples of such additives include, but are not limited, isopropyl myristate, ethyl acetate, C 12-05 alkyl benzoates, mineral oil, squalane, cyclomethicone, and capric/caprylic triglycerides.

Emulsions

[0139] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of an emulsion. Emulsions are heterogeneous systems of one liquid dispersed in another, typically in the form of droplets exceeding 0.1 pm in diameter. Emulsions are often biphasic systems comprising of two immiscible liquid phases intimately mixed and dispersed with each other. In general, emulsions may be either water-in-oil or of the oil-in-water variety. When an aqueous phase is finely divided into and dispersed as minute droplets into a bulk oily phase the resulting composition is called a water-in-oil emulsion. Alternatively, when an oily phase is finely divided into and dispersed as minute droplets into a bulk aqueous phase the resulting composition is called an oil- in-water emulsion. In some embodiments, the topical formulation comprises an oil-in-water emulsion. Emulsions may contain additional components in addition to the dispersed phases and the active drug may be present as a solution in the aqueous phase, oily phase, or itself as a separate phase. Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil-in-water-in-oil and water-in-oil-in- water emulsions. Either of the phases of the emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams.

[0140] Pharmaceutical excipients such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed. Suitable emulsifiers are well known in the art and are further described in Idson, Pharmaceutical Emulsions , in Pharmaceutical Dosage Forms , Marcel Dekker, Inc., New York, N.Y, 1988, volume 1, pp. 199-244; and U.S. Pat. No. 6,287,860, both incorporated by reference herein. Likewise, surfactants, also known as surface active agents, have found wide applicability in the formulation of emulsions and are well known in the art and are further described in Rieger, Surfactants , in Pharmaceutical Dosage Forms , Marcel Dekker, Inc., New York, N.Y, 1988, volume 1, pp. 285-366; and U.S. Pat. No. 6,287,860, both incorporated by reference herein. [0141] A large variety of non-emulsifying materials can also be included in emulsion formulations, including, but not limited to: fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives, and antioxidants (see Block, Emulsions and Microemulsions, in Pharmaceutical Dosage Forms , L Marcel Dekker, Inc., New York, N.Y, 1988, volume 1, pp. 335-378; and Idson, Pharmaceutical emulsions , in Pharmaceutical Dosage Forms , Marcel Dekker, Inc., New York, N.Y, 1988, volume 1, pp. 199-244).

[0142] Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersed-phase droplets and by increasing the viscosity of the external phase.

[0143] In some embodiments, the anti-infective composition is formulated as an emulsion and comprises a preservative. Since emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols, and phosphatides that may readily support the growth of microbes, these formulations often incorporate preservatives. Commonly used preservatives included in emulsion formulations include methyl paraben, propyl paraben, quaternary ammonium salts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boric acid.

Antioxidants are also commonly added to emulsion formulations to prevent deterioration of the formulation. Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabi sulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin.

[0144] In some embodiments, the anti-infective composition is formulated as a microemulsion. Microemulsions and their uses are well known in the art and are further described in Block, Emulsions and Microemulsions, in Pharmaceutical Dosage Forms, L Marcel Dekker, Inc., New York, N.Y, 1988, volume 1, pp. 335-378; and U.S. Pat. No. 6,287,860, both incorporated by reference herein.

Lotions and Creams

[0145] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of a cream or a viscous liquid. In some embodiments, creams are semisolid ( e.g. , soft solid or thick liquid) formulations that comprise an anti-infective composition dispersed in an oil-in-water emulsion or a water-in-oil emulsion as previously described. In some embodiments, a cream comprises an emulsifying agent and/or other stabilizing agents.

[0146] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition wherein the topical formulation is in the form of a lotion or low to medium viscosity liquid formulation. In some embodiments, lotions are fluid emulsions ( e.g ., oil-in-water emulsions or water-in-oil emulsions). The fluidity of lotions permits rapid and uniform application over a wide surface area of the skin. Lotions are typically intended to dry on the skin leaving a thin coat of their medicinal components on the skin’s surface. In some cases, a lotion comprises an emulsifying agent and/or other stabilizing agent. In some embodiments, the hydrophobic component of a lotion or cream is derived from an animal (e.g., lanolin, cod liver oil, or ambergris), plant (e.g, safflower oil, castor oil, coconut oil, cottonseed oil, menhaden oil, palm kernel oil, palm oil, peanut oil, soybean oil, rapeseed oil, linseed oil, rice bran oil, pine oil, sesame oil, or sunflower seed oil), or petroleum product (e.g, mineral oil or petroleum jelly). Ointments

[0147] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of an ointment. In some

embodiments, ointments are semisolid preparations that soften or melt at body temperature. In some embodiments, the topical formulation comprises an ointment base. In some embodiments, the ointment base is an oleaginous base, an absorption base, a water-in-oil emulsion base, an oil- in-water emulsion base, or a water soluble or water miscible base. In some embodiments, the base includes, but is not limited to, liquid paraffin, white petrolatum, waxes, esters of fatty alcohols, saturated fatty acids, oleic acid, olive oil, starch glycerin, purified lanolin, cetyl alcohol, glyceryl monostearate, methylparaben, propylparaben, glycol ethers, gelation hydrocarbon, polyethylene glycol, polyoxyl 40 stearate, polysorbates, hydrophilic ointment base, white ointment base, absorptive ointment base, Macrogol ointment base, simple ointment base, and the like. In some embodiments, the base includes liquid paraffin, white petrolatum, purified lanolin, gelation hydrocarbon, polyethylene glycol, hydrophilic ointment base, white ointment base, absorptive ointment base, Macrogol ointment base, simple ointment base, and the like. In some embodiments, the base includes liquid paraffin, white petrolatum, purified lanolin, gelation hydrocarbon, a polyethylene glycol, hydrophilic ointment base, white ointment base, simple ointment base, and mixtures thereof.

Liposomes

[0148] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of a liposome, nanoparticle, microsphere, microparticle, nanocapsule, or other agent which enhances or facilitates localized delivery to the skin. An example of a conventional microencapsulation process for

pharmaceutical preparations is shown in U.S. Pat. No. 3,737,337, incorporated by reference herein. A liposome is a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers. Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior that contains the composition to be delivered. Liposomal formulations are well known in the art and are further described in U.S. Pat. No. 6,287,860, incorporated by reference herein.

Foams

[0149] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of a foam. Topically suitable foams include formulations such as, but not limited to, emulsions, microemulsions, creams, and liposomes. While basically similar in nature, these formulations vary in the components and the consistency of the final product. The preparation of such compositions and formulations is generally known to those skilled in the pharmaceutical and formulation arts and may be applied to the formulation of the anti -infective compositions disclosed herein. In some embodiments, the foam comprises an emulsion in combination with a gaseous and/or pressurized propellant.

Pastes

[0150] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of a paste. In some embodiments a substance that behaves like a solid at room temperature until a sufficiently large load or stress is applied, at which point it flows like a fluid. Pastes are semisolid preparations that generally contain a large amount of finely powdered solids including, but not limited to: starch, zinc oxide, or calcium carbonate. In some embodiments, the paste contains at least 20% solids.

Sticks

[0151] Disclosed herein, in some embodiments, are topical formulations of an anti -infective composition, wherein the topical formulation is in the form of a stick. In some embodiments, sticks are solid dosage forms that melt at body temperature. In some embodiments, a stick comprises a wax, a polymer, a resin, or dry solid fused into a firm mass, and/or fused crystals. In some embodiments, a topical formulation of an anti-infective composition is in the form of a styptic pencil (i.e., a stick prepared by (1) heating crystals until they become molten, and (2) pouring the molten crystals into molds and allowing them to harden). In some embodiments, a topical formulation of an anti-infective composition is in the form of stick wherein the stick comprises a wax ( e.g ., the wax is melted and poured into appropriate molds in which they solidify in stick form).

[0152] In some embodiments, a topical formulation of an anti -infective composition is in the form of stick, wherein the stick comprises a melting base (i.e., a base that softens at body temperature). Examples of melting bases include, but are not limited to, waxes, oils, polymers and gels. In some embodiments, a topical formulation of an anti-infective composition is in the form of stick, wherein the stick comprises a base that is activated by the addition of moisture. Carriers and Excipients

[0153] The topical formulations disclosed herein are formulated in any suitable manner for application to the skin or a solid object. Any suitable technique, carrier, and/or excipient is contemplated for use with the topical formulations disclosed herein. Non-limiting examples of cosmetic, dermatological, or pharmaceutically acceptable carriers and excipients suitable for topical formulation can be found, for example, in Remington: The Science and Practice of Pharmacy , Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington’s Pharmaceutical Sciences , Mack Publishing Co., Easton, Pennsylvania 1975;

Liberman, H. A. and Lachman, L., Eds., Pharmaceutical Dosage Forms , Marcel Decker, New York, N.Y., 1980; Pharmaceutical Dosage Forms and Drug Delivery Systems , Eighth Ed.

(Lippincott Williams & Wilkins 2004); and Muller, R.H., et al. , Advanced Drug Delivery Reviews 59 (2007) 522-530, each of which is incorporated by reference in its entirety.

[0154] In some embodiments, the pharmaceutically acceptable carriers or excipients disclosed herein include, but are not limited to one or more: pH modifying agent (e.g, buffering agents), stabilizing agents, thickening agents, colorant agents, preservative agents, emulsifying agents, solubilizing agents, antioxidant agents, or any combination thereof. Other suitable compounds contemplated herein and within the knowledge of a practitioner skilled in the relevant art are found in the Handbook of Pharmaceutical Excipients, 4th Ed. (2003), the entire content of which is incorporated by reference herein.

[0155] In some embodiments, the topical formulations disclosed herein comprise additional ingredients, such as penetration enhancers, oils, waxy compounds, surfactants, stabilizers, gelling agents, moisturizers, water, or preservatives. In some embodiments, the topical formulations disclosed herein comprise one or more penetration enhancers to enhance delivery to the skin. Penetration enhancers may generally be classified as belonging to one of five broad categories, e.g, surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants. Penetration enhancers are well known in the art and are further described in U.S. Pat. No.

6,287,860, incorporated by reference herein. Exemplary penetration enhancers include, but are not limited to, sodium lauryl sulfate, sodium laurate, polyoxyethylene-20-cetyl ether, laureth-9, sodium dodecyl sulfate, dioctyl sodium sulfosuccinate, polyoxyethylene-9-lauryl ether (PLE), Tween 80, nonylphenoxypolyethylene (NP-POE), polysorbates, sodium glycocholate, sodium deoxycholate, sodium taurocholate, sodium taurodihydrofusidate, sodium glycodihydrofusidate, oleic acid, caprylic acid, mono- and di-glycerides, lauric acids, acylcholines, caprylic acids, acylcarnitines, sodium caprates, EDTA, citric acid, salicylates, DMSO, decylmethyl sulfoxide, ethanol, isopropanol, propylene glycol, polyethylene glycol, glycerol, propanediol, diethylene glycol monoethyl ether, urea, (carbonyldiamide), imidurea, N,N-diethylformamide, N-methyl-2- pyrrolidine, l-dodecal-azacyclopheptane-2-one, calcium thioglycate, 2-pyyrolidine, N,N-diethyl- m-toluamide, oleic acid and its ester derivatives, such as methyl, ethyl, propyl, isopropyl, butyl, vinyl and glycerylmonooleate, sorbitan esters, such as sorbitan monolaurate and sorbitan monooleate, other fatty acid esters such as isopropyl laurate, isopropyl myristate, isopropyl palmitate, diisopropyl adipate, propylene glycol monolaurate, propylene glycol monooleatea and non-ionic detergents such as BRIJ® 76 (stearyl poly(10 oxyethylene ether), BRIJ® 78 (stearyl poly(20)oxy ethylene ether), BRIJ® 96 (oleyl poly(10)oxy ethylene ether), and BRIJ® 721 (stearyl poly (21) oxyethylene ether), glyceryl monocaprylate/caprate, vitamin E TPGS (Eastman Chemical Company, Kingsport, Tenn.) and other tocopherol derivatives as described in U.S. Pat. No. 6,193,985. Additional exemplary penetration enhancers are described in Smith and Maibach (eds.), Percutaneous Penetration Enhancers, CRC Press, Inc., Boca Raton, Fla. (1995), which surveys the use and testing of various skin penetration enhancers, and Buyuktimkin, et al ., Chemical Means of Transdermal Drug Permeation Enhancement in Transdermal and Topical Drug Delivery Systems, Gosh T. K., Pfister W. R., Yum S. I. (Eds.), Interpharm Press Inc., Buffalo Grove, I. L. (1997).

[0156] In some embodiments, the topical formulations disclosed herein comprise one or more oils, waxy compounds, gelling agents, or surfactants. In some embodiments, the oils, waxy compounds, gelling agents and surfactants selected for the formulation and stabilization of the anti-infective composition are those traditionally employed in the dermatological arts. In some embodiments, the optional oils and/or waxy compounds constitute from 0.5% to 99.9% of the total weight of the composition. The amount of oil and/or wax depends on the actual form or physical state of the composition. Exemplary oils include, but are not limited to: mineral oils (petrolatum); vegetable oils (sweet almond, macadamia, blackcurrant-pip oil); synthetic oils such as perhydrosqualene, fatty alcohols, acids or esters (octyl palmitate, isopropyl lanolate, triglycerides including those of capric/caprylic acids), oxy ethyl enated or oxypropylenated fatty esters and ethers; and silicone oils (cyclomethicone, polydimethylsiloxanes or PDMS) or fluorinated oils. Exemplary waxy compounds include jojoba oil, paraffin, carnauba wax, and beeswax.

[0157] In some embodiments, the topical formulations disclosed herein comprise a surfactant. Exemplary surfactants (emulsifying and coemulsifying) include, but are not limited to: the esters of fatty acids and polyethylene glycol (PEG), esters of fatty acids and glycerol (glyceryl stearate) or esters of fatty acids and sugar (sorbitan stearate), as well as the polyoxyethylenated or polyoxypropylenated derivatives thereof, cyclomethi cones and dimethicone copolyols, and also anionic surfactants (K or Na alkyl phosphate).

[0158] In some embodiments, the topical formulations disclosed herein comprise viscosity modifiers. If a viscosity modifier is present, in some embodiments, the viscosity modifier is present in amounts from about 0.01% to about 10% by weight of the composition. Viscosity modifiers such as cetyl alcohol, glycerol, polyethylene glycol (PEG), PEG-stearate, or Keltrol may also be used to enhance the stability of the formulation. Thickeners which may enhance the stability include gelling agents such as cellulose and derivatives, Carbopol and derivatives, carob, carregeenans and derivatives, xanthane gum, sclerane gum, long chain alkanolamides, bentone and derivatives, Kaolin USP, Veegum Ultra, Green Clay, Bentonite NFBC, magnesium aluminum silicate (Veegum^®), guar gums (such as Jaguar HP-120^®), xanthan gum, sodium carboxymethyl cellulose, hydroxyalkyl and alkyl celluloses, cross-linked acrylic acid polymers, and mixtures thereof. As known to those skilled in the art, the precise amount of thickeners can vary depending upon the desired consistency and thickness of the composition.

[0159] In some embodiments, the topical formulations disclosed herein comprise one or more moisturizers. As used herein, a“moisturizer” is an ingredient which promotes the retention of water to the surface area of the human body, including hair and skin. The term moisturizer as used herein includes both components which deliver water to the skin, also commonly referred to as a“humectant,” and components which prevent the loss of water from the skin, also commonly referred to as an“occlusive.” Exemplary moisturizers include, but are not limited to: wheat protein ( e.g ., laurdimonium hydroxypropyl hydrolyzed wheat protein), hair keratin amino acids, sodium peroxylinecarbolic acid, panthenol, tocopherol (Vitamin E), dimethicone, polyhydroxy alcohols, including butylene glycol, hexylene glycol, propylene glycol, sorbitol and the like; lactic acid and lactate salts, such as sodium or ammonium salts; C3 and C₆ diols and triols including hexylene glycol, 1,4 dihydroxyhexane, 1,2,6-hexane triol; aloe vera in any of its forms, for example aloe vera gel; sugars and starches; sugar and starch derivatives, for example alkoxylated glucose; hyaluronic acid; lactamide monoethanolamine; acetamide monoethanolamine; glycolic acid; alpha and beta hydroxy acids ( e.g ., lactic, glycolic salicylic acid); glycerine; pantheol; urea; vaseline; natural oils; and emollients.

[0160] In some embodiments, the topical formulations disclosed herein comprise one or more preservatives. The preservative, when utilized, is in an amount sufficient to extend the shelf-life or storage stability, or both, of the topical formulations disclosed herein. Exemplary

preservatives include, but are not limited to: tetrasodium ethylene-diamine tetraacetic acid (EDTA), methyl, ethyl, butyl, and propyl parabens, benzophenone-4,

methylchloroisothiazolinone, methylisothiazolinone, sodium benzoate, paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenyl ethyl alcohol, dehydroacetic acid, sorbic acid, benzalkonium chloride (BKC), benzethonium chloride, phenol, phenylmercuric nitrate, and thimerosal.

[0161] In some embodiments, the topical formulations disclosed herein comprise one or more gelling (or thickening) agents. In some embodiments, the topical formulations disclosed herein further comprise from about 0.1% to about 5%, more preferably from about 0.1% to about 3%, and most preferably from about 0.25% to about 2%, of a gelling agent. In certain embodiments, the viscosity of a topical formulation disclosed herein is in the range from about 100 to about 500,000 cP, about 100 cP to about 1,000 cP, about 500 cP to about 1500 cP, about 1000 cP to about 3000 cP, about 2000 cP to about 8,000 cP, about 4,000 cP to about 10,000 cP, about 10,000 cP to about 50,000 cP.

[0162] Suitable gelling agents for use in preparation of the gel topical formulation include, but are not limited to: celluloses, cellulose derivatives, cellulose ethers (e.g., carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropyl cellulose, methylcellulose), guar gum, xanthan gum, locust bean gum, alginates (e.g, alginic acid), silicates, starch, tragacanth, carboxyvinyl polymers, carrageenan, paraffin, petrolatum, acacia (gum arabic), agar, aluminum magnesium silicate, sodium alginate, sodium stearate, bladderwrack, bentonite, carbomer, carrageenan, carbopol, xanthan, cellulose, microcrystalline cellulose (MCC), ceratonia, chondrus, dextrose, furcellaran, gelatin, ghatti gum, guar gum, hectorite, lactose, sucrose, maltodextrin, mannitol, sorbitol, honey, maize starch, wheat starch, rice starch, potato starch, gelatin, sterculia gum, polyethylene glycol (e.g, PEG 200-4500), gum tragacanth, ethyl cellulose, ethylhydroxyethyl cellulose, ethylmethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, poly(hydroxyethyl methacrylate), oxypolygelatin, pectin, polygeline, povidone, propylene carbonate, methyl vinyl ether/maleic anhydride copolymer (PVM/MA),

poly(methoxyethyl methacrylate), poly(methoxyethoxyethyl methacrylate), hydroxypropyl cellulose, hydroxypropylmethyl-cellulose (HPMC), sodium carboxymethyl-cellulose (CMC), silicon dioxide, polyvinylpyrrolidone (PVP/povidone), or combinations thereof. In some embodiments, the anti-infective composition is formulated for topical application and comprises 0.1-3% hydroxyethylcellulose (HE cellulose).

[0163] Suitable agents for use in the formulations described herein and that are applied as liquids and gel upon application to the skin into a film include, but are not limited to, polymers composed of polyoxypropylene and polyoxyethylene, which form thermoreversible gels when incorporated into aqueous solutions. These polymers have the ability to change from the liquid state to the gel state at temperatures close to body temperature, therefore allowing useful formulations that are applied as gels and/or films to the affected area. Examples of polymers that gel at body temperature and are used in the gels and/or films described herein include, but are not limited to, poloxamers ( e.g ., Pluronics F68^®, F88^®, F108^®, and F127^®, which are block copolymers of ethylene oxide and propylene oxide). The liquid state-to-gel state phase transition is dependent on the polymer concentration and the ingredients in the solution.

[0164] In some embodiments, the topical formulations disclosed herein comprise an emollient. Emollients include, but are not limited to, castor oil esters, cocoa butter esters, safflower oil esters, cottonseed oil esters, corn oil esters, olive oil esters, cod liver oil esters, almond oil esters, avocado oil esters, palm oil esters, sesame oil esters, squalene esters, kikui oil esters, soybean oil esters, acetylated monoglycerides, ethoxylated glyceryl monostearate, hexyl laurate, isohexyl laurate, isohexyl palmitate, isopropyl palmitate, methyl palmitate, decyloleate, isodecyl oleate, hexadecyl stearate decyl stearate, isopropyl isostearate, methyl isostearate, diisopropyl adipate, diisohexyl adipate, dihexyldecyl adipate, diisopropyl sebacate, lauryl lactate, myristyl lactate, and cetyl lactate, oleyl myristate, oleyl stearate, and oleyl oleate, pelargonic acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, hydroxystearic acid, oleic acid, linoleic acid, ricinoleic acid, arachidic acid, behenic acid, erucic acid, lauryl alcohol, myristyl alcohol, cetyl alcohol, hexadecyl alcohol, stearyl alcohol, isostearyl alcohol, hydroxystearyl alcohol, oleyl alcohol, ricinoleyl alcohol, behenyl alcohol, erucyl alcohol, 2-octyl dodecanyl alcohol, lanolin and lanolin derivatives, beeswax, spermaceti, myristyl myristate, stearyl stearate, carnauba wax, candelilla wax, lecithin, and cholesterol.

[0165] In some embodiments, the topical formulations disclosed herein comprise abrasives, absorbents, anticaking agents, astringents, essential oils, fragrances, skin-conditioning agents, skin healing agents, skin protectants (e.g., sunscreens, or ultraviolet light absorbers or scattering agents), skin soothing agents, preservatives, or any combinations thereof. [0166] In some embodiment, the topical formulations disclosed herein comprise one or more fragrances. As used herein, the term“fragrance” is meant to encompass any component reacting with the human olfactory sites and imparting a pleasurable odor, essence, or scent. Fragrances that may be used in the topical formulations disclosed herein include any synthetic or natural fragrance, as well as any mixtures thereof. In some embodiments, multiple fragrances are used to achieve the desired effect.

[0167] Fragrances suitable for use in the disclosed topical formulations include, but are not limited to: linear and cyclic alkenes (i.e., terpenes); primary, secondary and tertiary alcohols; ethers; esters; ketones; nitrites; and saturated and unsaturated aldehydes; or mixtures

thereof. Exemplary synthetic fragrances suitable for use in the disclosed topical formulations include, but are not limited to one or more of: acetanisole; acetophenone; acetyl cedrene; methyl nonyl acetaldehyde; musk anbrette; heliotropin; citronellol; sandella; methoxycitranellal;

hydroxycitranellal; phenyl ethyl acetate; phenylethylisobutarate; gamma methyl ionone; geraniol; anethole; benzaldehyde; benzyl acetate; benzyl salicate; linalool; cinnamic alcohol; phenyl acetaldehyde; amyl cinnamic aldehyde; caphore; p-tertiairy butyl cyclohexyl acetate; citral;

cinnamyl acetate; citral diethyl acetal; coumarin; ethylene brasslate; eugenol; 1 -menthol; and vanillin. Natural fragrances suitable for use in the disclosed topical formulations include, but are not limited to one or more of: lavandin; heliotropin; sandlewood oil; oak moss; pathouly;

ambergris tincture; ambrette seed absolute; angelic root oil; bergamont oil; benzoin Siam resin; buchu leaf oil; cassia oil; cedar-wood oil; cassia oil; castoreum; civet absolute; chamomile oil; geranium oil; lemon oil; lavender oil; and Ylang Ylang oil. See Perfume and Flavor Chemicals , Vols. I and II; Steffen Arctander Allured Pub. Co. (1994) and Perfumes: Art, Science and Technology ; Muller, P. M. and Lamparsky, D., Blackie Academic and Professional (1994), both incorporated herein by reference, for a more detailed description of fragrances suitable for use in the topical formulations disclosed herein.

EXAMPLES

The following examples are illustrative and non-limiting to the scope of the compositions, methods, and formulations described herein.

Example 1 - Neutralizing Antibodies are Stable and Show no Reduction in Efficacy after Incubation at Room Temperature

[0168] Neutralizing antibodies targeting either the influenza A HA protein variable head region

(PY102) or the conserved stalk region (6F12) have been characterized and shown to elicit protection against influenza viruses both in vitro and in vivo. See DeLillo, el al ., Nat. Med., Feb

2014, 20(2): 143—151. The anti-Hl globular head neutralizing antibody PY102 is strain specific and only neutralizes the PR8 H1N1 strain (PR8) of influenza virus. In contrast, the anti-stalk neutralizing antibody 6F12 has been shown to neutralize a broad selection of epidemic HI influenza viruses, including the 2009 pandemic H1N1 strains. Here, neutralizing antibodies PY102 and 6F12 were combined with a colloidal substance to determine their therapeutic potential as an influenza prophylactic. Viral infection was measured via a plaque assay in Madin Darby canine kidney (MDCK) cells with a lack of plaque formation indicative of virus neutralization.

[0169] An initial in vitro influenza neutralization assay was performed and the efficacy of neutralizing antibodies PY102 and 6F12 was tested against H1N1 influenza A strain PR8, where PY102 was found to be more potent than 6F12. Next, the cytotoxicity of 2.2%

hydroxyethylcellulose (HE cellulose) was tested and found to be non-cytotoxic based upon the microscopic examination of HE cellulose treated MDCK cells.

[0170] After optimization of these parameters, the antibodies were tested in conjunction with HE cellulose and PR8 plaques were counted. Briefly, the antibodies were diluted in 2.2% HE cellulose, incubated at room temperature (RT) for up to 2 weeks, and dispersed throughout a 12- well tissue-cultured plate. PR8 was diluted to 6.7 x 10 ³ pfu/ml then incubated with the antibody/HE cellulose mixture on a rotator for 1 hour at RT. This mixture was then added dropwise on wild-type MDCK cells that were seeded in 12-well tissue-cultured plates at 1.75 x 10⁵ cells/well and incubated 24h prior in a 5% CO2, 37°C incubator.

[0171] Cells were treated as described in Table 1 for an hour in a 5% C02, 37°C incubator. Cells were then overlaid with agar solution containing 1 pg/mL TPCK trypsin and incubated for 48 hours in a 5% C02, 37°C incubator. The plates were subsequently fixed with 4%

paraformaldehyde for 15 minutes at RT, the agar was removed, 1ml of Crystal Violet was added, and the plates were incubated at RT for 30 minutes and washed with water. The plates were then photographed and the plaques counted. As seen in FIGS. 1-2, both 6F12 and PY102 neutralized PR8 plaque formation indicating that the antibodies were stable at room temperature for at least 2 weeks in 2.2% HE cellulose.

[0172] Compared to virus only, inhibition of Influenza A PR8 by 2pg/mL 6F12 or PY102 ranged from 90%-100%. PY102 and 6F12 antibodies successfully neutralized PR8 virus when diluted in PBS or HE cellulose, were stable at RT for at least 2 weeks when diluted in PBS or 2.2% HE cellulose, and did not display any loss in efficacy at either RT or 37°C. Table 1. Viral Plaque Assay

Example 2 - Neutralizing Antibodies are Stable and Show no Reduction in Efficacy after Incubation at 37°C or Prolonged Incubation at Room Temperature

[0173] An anti -infective composition comprising neutralizing antibodies ( e.g ., PY102, 6F12, or any other influenza neutralizing antibody disclosed herein) is diluted in 2.2% HE cellulose as described in Example 1 and incubated at either room temperature or 37°C for a period of 1 month, 3 months, 6 months, or 12 months at either room temperature or 37°C. After the incubation period, virus is added as described in Example 1, and the efficacy of the anti -infective composition is assessed as described in Example 1 or 3 respectively. Optionally, the anti- infective composition is formulated as one or more of the topical formulations disclosed herein prior to the extended incubation period.

Example 3 - ELISA Assay

[0174] The effectiveness of the neutralizing antibodies described herein is assessed by measuring the amount of antibodies bound to viral proteins as a surrogate of neutralization capacity by enzyme-linked immunosorbent assay (ELISA). Any suitable method can be used to perform the ELISA. In some embodiments, an ELISA assay is utilized to measure the amount of influenza virus HA and/or NA antigen present in a sample as a supplement or substitute to a viral plaque assay.

Example 4 - Neutralizing Antibodies Applied to the Surface of the Skin Effectively

Neutralize Influenza Virus

[0175] Mice are divided into 3 groups and the hair on the dorsal skin is removed by shaving, chemical treatment, or both. Alternatively, athymic nude mice ( e.g ., Foxnl -mx\\ mice) can be utilized to avoid the need to remove hair from the dorsal skin. For the test group and negative control group, neutralizing antibodies (e.g., PY102, 6F12, or any other influenza neutralizing antibody disclosed herein) in a formulation suitable for topical application (e.g, 2.2% HE) are applied to the dorsal skin and allowed to incubate on the skin at room temperature for a period of 1-2 hours. For the positive control group, a topical formulation lacking neutralizing antibodies is applied to the dorsal skin and allowed to incubate on the skin at room temperature for a period of 1-2 hours. The test group and negative control group mice are then immobilized, and influenza virus (e.g, PR8) is applied to the same area of the dorsal skin as the neutralizing antibody. No influenza virus is added to the dorsal skin of the negative control group. After a viral incubation period, the virus is collected from the surface of the skin and neutralization efficacy is assessed by serial dilution plaque assay or ELISA as described in Examples 1 and 3 respectively.

Example 5 - Lyophilization and Reconstitution Studies

[0176] An anti -infective composition comprising neutralizing antibodies is lyophilized by any suitable lyophilization procedure known in the art. The lyophilized anti -infective composition is then stored for a period of 0 hours, 2 hours, 12 hours, 24 hours, 2 days, 7 days, 14 days, 1 month, 3 months, and 6 months at either room temperature or 37°C. After the respective storage period, the anti -infective composition is reconstituted into an aqueous solution and neutralization efficacy is assessed by serial dilution plaque assay or ELISA as described in Examples 1 and 3 respectively. Optionally, the reconstituted anti-infective composition is formulated as one or more of the topical formulations disclosed herein prior to the neutralization assay.

Example 6 - Topical Formulation of a Neutralizing Antibody

[0177] A topical formulation of an anti-infective composition comprising a neutralizing antibody (e.g, PY102, 6F12, or any other influenza neutralizing antibody disclosed herein) is prepared by diluting the neutralizing antibody from 0.1- 5.0 mg/ml in 5 mM phosphate, pH 6.0. In some embodiments EDTA or any other suitable preservative is added. Example 7 - Topical Cream Formulation of a Neutralizing Antibody

[0178] A topical formulation of an anti -infective composition comprising a neutralizing antibody ( e.g ., PY102, 6F12, or any other influenza neutralizing antibody disclosed herein) in the form of a cream is prepared by suspending the anti-infective composition in water, adding Span 85 followed by addition of glycerin, mineral oil, and other excipients.

Table 2. Cream Formulation

Example 8 - Topical Lotion Formulation of a Neutralizing Antibody

[0179] A topical formulation of an anti -infective composition comprising a neutralizing antibody (e.g., PY102, 6F12, or any other influenza neutralizing antibody disclosed herein) in the form of a lotion is prepared by suspending the anti -infective composition in water in the following formulation:

Table 3. Topical Lotion Formulation

Example 9 - Topical Hydrogel Formulation of a Neutralizing Antibody

[0180] A topical formulation of an anti -infective composition comprising a neutralizing antibody ( e.g ., PY102, 6F12, or any other influenza neutralizing antibody disclosed herein) in the form of a hydrogel is prepared by adding a diluted, aqueous anti-infective composition, benzyl alcohol, and glycerin to about 3200 mL of purified water. Carbopol is slowly added to the mixture. The volume is brought up to 4000 mL with purified water. Finally, a neutralizing agent (e.g., sodium hydroxide, potassium hydroxide, or triethanolamine) is added dropwise until a gel is formed.

Table 4. Gel Formulation #1

[0181] A topical formulation of an anti -infective composition comprising a neutralizing antibody (e.g, PY102, 6F12, or any other influenza neutralizing antibody disclosed herein) in the form of a hydrogel is prepared as indicated in Table 5 below.

Table 4. Gel Formulation #2

Example 10 - Evaluation of Blockade Antibody Titers after Multivalent Norovirus VLP Immunization

[0182] Three goats were immunized with human norovirus multivalent virus-like particle (VLP) cocktails representing GI.3 DSV (GI.3), GI.4 Chiba (GI.4), GII.4 2012 Sydney (GII.4 2012) and GII.2 SMV (GII.2) strains. Sera from pre-immune bleeds and bleeds 1-4 following immunization were evaluated for blockade antibody titer (mean IC50) against the four immunizing VLPs (FIGS. 3-6 and Table 5). Enzyme immunoassay plates were coated with 10 pg/ml porcine gastric mucin (PGM) type III (all VLP except GII.2 SMV) or human type B saliva (GII.2 SMV) diluted in PBS and blocked with 5% Blotto in PBS-0.05% Tween 20. VLPs (0.25 pg/ml) were pretreated with decreasing two-fold concentrations of serum for 1 hour before being added to the PGM-coated plates for 1 hour. Ligand-bound VLP were detected with rabbit anti-VLP hyper-immune serum followed by anti-rabbit-IgG-HRP and color developed with TMB substrate. Incubations were done at 37° C. The percent control binding was defined as binding in the presence of antibody pretreatment divided by binding in the absence of antibody pretreatment multiplied by 100.

Multivalent immunization resulted in generation of blockade antibodies against all four vaccine components VLPs: GI.3, GI.4, GII.4 2012 and GII.2. Blockade antibody titers did not increase after bleed 3. A similar lack of titer increase after multiple exposures has been observed in humans vaccinated with norovirus VLPs. Sera from bleed 4 were pooled (“Pool”) and titers were measured. Serum collected before immunization (pre-immune) did not block VLP binding even at 1/500 dilution, the lowest dilution tested.

Table 5. Comparison of Goat Hyper-Immune Sera and Human Convalescent Sera

Blockade Titer by VLP

[0183] Serum titers in the immunized goats were compared to titers in human norovirus convalescent serum as a proxy measure of the protective level of blockade antibodies (Table 5). Genogroup I VLP GI.3 and GI.4 (heterotypic VLP) titers were compared to titers of serum from a GI. l (homotypic) infected individual. GII.4 2012 (homotypic VLP) and GII.17 (heterotypic VLP) titers were compared to titers from convalescent serum from a GII.4 2015 infection. GII.2 goat sera titers were compared to titers in GII.2 infected convalescent serum. Blockade antibody titer dilution IC50 to non-immunogen, cross-genogroup VLPs was less than 500-fold.

[0184] IgG from the pooled sera was purified and lyophilized as described in Example 5.

Blockade antibody titers against the four immunizing VLPs were measured before and after gamma irradiation, with and without inclusion of lotion base (FIG. 7 and Table 6). Lotion dilutions start at 25%, the most concentrated dilution that could be accurately pipetted. The lotion was diluted across the plate with the antibody allowing comparison of the antibody versus lotion effect at each dilution. Lotion only was tested one time in duplicate. The final purified, irradiated IgG retained blockade potency for the immunizing VLP. While the lotion base alone inhibited VLP binding to ligand, it did not notably interfere or enhance antibody inhibition of VLP binding to ligand at 25%. Table 6. ICso Titers for Blockade of Immunizing VLPs with or without 25% Lotion Base

[0185] Even at 1/500 dilution blockade antibody potency did not extend to VLPs of genotypes in genogroups I and II not included in the immunization cocktail. However, vaccination did stimulate cross-blockade antibody production within genogroup GII.4 (FIGS. 6E, and 8; Tables 5, 7 and 8). The final product (“AvLo”), containing purified, irradiated IgG and lotion base and stored at room temperature, retained blockade antibody functionality against all immunizing VLPs as well as heterotypic GII.4 VLPs (FIG. 9 and Table 8).

Table 7. ICso Titers for Blockade of Non-Immunizing VLPs with or without 25% Lotion Base

Table 8. IC50 titers for AvLo Blockade of Norovirus Immunizing and Heterotypic GII.4 VLPs Binding to Ligand

[0186] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention.

It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMS WHAT IS CLAIMED IS:

1. An anti -infective composition comprising an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti -infective composition reduces the risk of absorption, infectivity, or transmission of a pathogen.

2. The anti-infective composition of claim 1, wherein the neutralizing antibody is a broadly neutralizing antibody (bNAb).

3. The anti-infective composition of claim 1, wherein the anti-infective composition comprises a mixture of two or more neutralizing antibodies.

4. The anti-infective composition of claim 1, wherein the anti-infective composition further comprises an additional anti -infective agent.

5. The anti-infective composition of claim 4, wherein the additional anti -infective agent comprises an aminoglycoside, beta-lactam, amphenicol, fluoroquinolone, fusidic acid, glycopeptide, macrolide, lincosamide, mupirocin, polymixin, sulfonamide, tetracycline, antibacterial antibody, antibacterial peptide, or any combinations thereof.

6. The anti-infective composition of claim 4, wherein the additional anti-infective active agent is conjugated to the neutralizing antibody.

7. The anti-infective composition of claim 4, wherein the additional anti-infective agent comprises bacitracin, polymyxin B, neomycin, or any combinations thereof.

8. The anti-infective composition of claim 1, wherein anti-infective composition is formulated as an aqueous or non-aqueous solution or liquid, spray, aerosol, gel, powder, emulsion, suspension, lotion, cream, ointment, foam, oil, liposome, nanoparticle, paste, or stick.

9. The anti-infective composition of claim 1, wherein the neutralizing antibody neutralizes a respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus, influenza virus, parainfluenza virus, coronavirus, norovirus, rotavirus, hepatitis A virus, adenovirus, astrovirus, S. aureus , methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterococcus spp ., Enter obacter spp ., C. difficile , Campylobacter, E. faecali, E.faecium , or Salmonella.

10. The anti-infective composition of claim 9, wherein the neutralizing antibody (a) neutralizes at least one strain of a group 1 influenza A virus, (b) neutralizes at least one strain of a group 2 influenza A virus, or (c) neutralizes at least one strain of an influenza B virus.

11. The anti-infective composition of claim 10, wherein the neutralizing antibody binds an epitope in the influenza virus hemagglutinin (HA) protein.

12. The anti-infective composition of claim 11, wherein the HA protein is HI, H2, H3, H4, H5, H6, H7, H8, H9, H10, HI 1, H12, H13, H14, H15, H16, H17, H18, or influenza B HA.

13. The anti-infective composition of claim 11, wherein the neutralizing antibody binds an epitope in the globular head domain (HA1) of the influenza virus HA protein.

14. The anti-infective composition of claim 11, wherein the neutralizing antibody binds an epitope in the stem domain (HA2) of the influenza virus HA protein.

15. The anti-infective composition of claim 11, wherein the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple strains of the same influenza A subtype.

16. The anti-infective composition of claim 11, wherein the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple influenza A HI strains.

17. The anti-infective composition of claim 11, wherein the neutralizing antibody binds an epitope in the influenza HA protein and (a) neutralizes a viral strain from more than one group 1 influenza A subtype; (b) neutralizes a viral strain from more than one group 2 influenza A subtype; or (c) neutralizes a viral strain from more than one influenza B lineage.

18. The anti-infective composition of claim 17, wherein the neutralizing antibody binds an epitope in the influenza HA protein and (a) neutralizes a viral strain from all group 1 influenza A subtypes; (b) neutralizes a viral strain from all group 2 influenza A subtypes; or (c) neutralizes a viral strain from all group 1 and group 2 influenza A subtypes.

19. The anti-infective composition of claim 17, wherein the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from both the Yamagata and Victoria influenza B lineages.

20. The anti-infective composition of claim 17, wherein the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes a viral strain from: (a) all group 1 influenza A subtypes; (b) all group 2 influenza A subtypes; and (c) both the Yamagata and Victoria influenza B lineages.

21. The anti-infective composition of claim 11, wherein the neutralizing antibody binds an epitope in a viral strain of: influenza A H1N1, influenza A H3N2, influenza B Yamagata, influenza B Victoria, or any combinations thereof.

22. The anti-infective composition of claim 11, wherein the anti-infective composition comprises a mixture of three or more neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in a Group 1 influenza A viral strain; (b) one or more neutralizing antibodies binds an epitope in a Group 2 influenza A viral strain; and (c) one or more neutralizing antibodies binds an epitope in an influenza B Yamagata lineage or Victoria lineage viral strain.

23. The anti-infective composition of claim 11, wherein the anti-infective composition comprises a mixture of two or more neutralizing antibodies, wherein: (a) one or more

neutralizing antibodies binds an epitope in a Group 1 influenza A viral strain or a Group 2 influenza A viral strain; and (b) one or more neutralizing antibodies binds an epitope in an influenza B Yamagata lineage or Victoria lineage viral strain.

24. The anti-infective composition of claim 11, wherein the neutralizing antibody is PY102, 6F12, CR6261, C179, CR8020, CR8043, CR8033, CR8071, F10, FI6, a FI6 variant, CR9114, 81.39, or any combinations thereof.

25. The anti-infective composition of claim 9, wherein the neutralizing antibody neutralizes a respiratory syncytial virus (RSV) subgroup A or subgroup B virus.

26. The anti-infective composition of claim 25, wherein the neutralizing antibody that binds an epitope in the RSV attachment protein (G) or fusion protein (F).

27. The anti-infective composition of claim 26, wherein the neutralizing antibody that binds an epitope in the RSV F protein, wherein the neutralizing antibody neutralizes both RSV subgroup A and RSV subgroup B viruses.

28. The anti-infective composition of claim 26, wherein the neutralizing antibody binds an epitope in antigenic region I, II, IV, or 0 of the RSV F protein.

29. The anti-infective composition of claim 26, wherein the neutralizing antibody is 54G10, MAbl9, 1308F, chlOlF, 5C4, D25, MPE8, AM14, AM16, AM23, palivizumab motavizumab, or any combinations thereof.

30. The anti-infective composition of claim 9, wherein the neutralizing antibody neutralizes a human metapneumovirus (hMPV) subgroup Al, A2, Bl, or B2 virus.

31. The anti-infective composition of claim 30, wherein the neutralizing antibody binds an epitope in the hMPV attachment protein (G) or fusion protein (F).

32. The anti-infective composition of claim 30, wherein the neutralizing antibody that binds an epitope in the hMPV F protein, and wherein the neutralizing antibody neutralizes subgroup Al, A2, Bl and B2 hMPV viruses.

33. The anti-infective composition of claim 30, wherein the neutralizing antibody binds an epitope in epitope groups 2, 3, 4, 5, and 6 of the hMPV F protein.

34. The anti-infective composition of claim 30, wherein the neutralizing antibody is 54G10, DS7, MAb 338, MAb 234, MAb 628, or any combinations thereof.

35. The anti-infective composition of claim 9, wherein the neutralizing antibody binds an epitope in a Pneumovirinae family virus F protein and neutralizes both RSV and hMPV.

36. The anti-infective composition of claim 35, wherein the neutralizing antibody is 54G10 or MPE8.

37. The anti-infective composition of claim 9, wherein the neutralizing antibody binds an epitope in a GII.4 genotype norovirus.

38. The anti-infective composition of claim 37, wherein the neutralizing antibody binds an epitope in the major capsid protein of a GII.4 norovirus.

39. The anti-infective composition of claim 38, wherein the neutralizing antibody binds an epitope in the P domain of the major capsid protein of a GII.4 norovirus.

40. The anti-infective composition of claim 39, wherein the neutralizing antibody is NVB 71.4 or GII.4.2002. G5.

41. An anti -allergic composition comprising an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti -allergic composition reduces the risk of an allergic reaction upon exposure to an allergen or environmental contaminant.

42. The anti-allergic composition of claim 41, wherein the anti-allergic composition comprises a mixture of two or more neutralizing antibodies.

43. The anti-allergic composition of claim 41, wherein the anti-allergic composition is formulated as a aqueous or non-aqueous solution or liquid, spray, aerosol, gel, powder, emulsion, suspension, lotions, cream, ointment, foam, oil, liposome, nanoparticle, paste, or stick.

44. The anti-allergic composition of claim 41, wherein the allergic reaction is caused by a Toxicodendron species of plant, an alkylresorcinol, neomycin, or an environmental contaminant.

45. The anti-allergic composition of claim 41, wherein the neutralizing antibody comprises an anti-urushiol antibody.

46. The anti-allergic composition of claim 45, wherein the environmental contaminant is nickel, gold, or chromium.

47. A method of reducing the likelihood of a pathogenic infection comprising, applying an anti-infective composition to a dermal surface, wherein the anti -infective composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, and wherein the anti-infective composition reduces the risk of absorption, transmission, or infectivity of a pathogen.

48. A method of reducing the likelihood of transmission of a pathogenic infection

comprising, applying an anti-infective composition to the surface of a solid object, wherein the anti-infective composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient, and wherein the anti -infective composition reduces the risk of fomite driven pathogen transmission.

49. The method of claim 47 or 48, wherein the anti-infective composition comprises a mixture of two or more neutralizing antibodies.

50. The method of claim 47, wherein the anti -infective composition is applied to an individual’s hands, arms, torso, legs, or face.

51. The method of claim 47 or 48, wherein the anti-infective composition further comprises an additional anti-infective agent.

52. The method of claim 51, wherein the additional anti -infective active agent is an aminoglycoside, beta-lactam, amphenicol, fluoroquinolone, fusidic acid, glycopeptide, macrolide, lincosamide, mupirocin, polymixin, sulfonamide, tetracycline, antibacterial antibody, or antibacterial peptide.

53. The method of claim 51, wherein the additional anti -infective active agent is conjugated to the neutralizing antibody.

54. The method of claim 51, wherein the additional anti -infective agent is bacitracin, polymyxin B, neomycin, or any combinations thereof.

55. The method of claim 47 or 48, wherein anti -infective composition is formulated as an aqueous or non-aqueous solution or liquid, spray, aerosol, gel, powder, emulsion, suspension, lotion, cream, ointment, foam, oil, liposome, nanoparticle, paste, or stick.

56. The method of claim 48, wherein the solid object is a table, door knob or handle, banister or railing, elevator button, countertop, stovetop, cabinet or cabinet knob or handle, blanket, linen, towel, glove, mask or children’s toy.

57. The method of claim 48, wherein the solid object is an examination or surgical glove.

58. The method of claim 57, wherein the anti -infective composition is applied to the exterior or interior surface of the examination or surgical glove.

59. The method of claim 58, wherein the anti -infective composition is formulated as a powder, aerosol, spray, gel, emulsion, lotion, cream, or ointment and is applied to the hands or interior surface of the examination or surgical glove.

60. The method of claim 47 or 48, wherein the pathogenic infection is an infection of respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus, influenza virus, parainfluenza virus, coronavirus, norovirus, rotavirus, hepatitis A virus, adenovirus, astrovirus, S. aureus , methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterococcus spp. , Enter obacter spp. , C. difficile , Campylobacter, E.faecali, E.faecium , or Salmonella.

61. The method of claim 60, wherein the neutralizing antibody (a) neutralizes at least one strain of a group 1 influenza A virus; (b) neutralizes at least one strain of a group 2 influenza A virus; or (c) neutralizes at least one strain of an influenza B virus.

62. The method of claim 61, wherein the neutralizing antibody binds an epitope in the influenza virus hemagglutinin (HA) protein.

63. The method of claim 62, wherein the HA protein is HI, H2, H3, H4, H5, H6, H7, H8, H9, H10, HI 1, H12, H13, H14, H15, H16, H17, H18, or influenza B HA.

64. The method of claim 62, wherein the neutralizing antibody binds an epitope in the globular head domain (HA1) of the influenza virus HA protein.

65. The method of claim 62, wherein the neutralizing antibody binds an epitope in the stem domain (HA2) of the influenza virus HA protein.

66. The method of claim 62, wherein the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple strains of the same influenza A subtype.

67. The method of claim 62, wherein the neutralizing antibody binds an epitope in the influenza HA protein and neutralizes multiple influenza A HI strains.

68. The method of claim 62, wherein the neutralizing antibody binds an epitope in the influenza HA protein and (a) neutralizes a viral strain from more than one group 1 influenza A subtype; (b) neutralizes a viral strain from more than one group 2 influenza A subtype; or (c) neutralizes a viral strain from more than one influenza B lineage.

69. The method of claim 62, wherein the neutralizing antibody binds an epitope in the influenza HA protein and (a) neutralizes a viral strain from all group 1 influenza A subtypes; (b) neutralizes a viral strain from all group 2 influenza A subtypes; (c) neutralizes a viral strain from all group 1 and group 2 influenza A subtypes; or (d) neutralizes a viral strain from both the Yamagata and Victoria influenza B lineages.

70. The method of claim 69, wherein the neutralizing antibody binds an epitope in the influenza HA protein and (a) neutralizes a viral strain from all group 1 influenza A subtypes; (b) neutralizes a viral strain from all group 2 influenza A subtypes; and (c) neutralizes a viral strain from both the Yamagata and Victoria influenza B lineages.

71. The method of claim 61, wherein the neutralizing antibody binds an epitope in a viral strain of at least one of: influenza A H1N1, influenza A H3N2, influenza B Yamagata, or influenza B Victoria.

72. The method of claim 62, wherein the anti -infective composition comprises a mixture of three or more neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in a Group 1 influenza A viral strain; (b) one or more neutralizing antibodies binds an epitope in a Group 2 influenza A viral strain; and (c) one or more neutralizing antibodies binds an epitope in an influenza B Yamagata lineage or Victoria lineage viral strain.

73. The method of claim 62, wherein the anti -infective composition comprises a mixture of two or more neutralizing antibodies, wherein: (a) one or more neutralizing antibodies binds an epitope in a Group 1 influenza A viral strain and Group 2 influenza A viral strain; and (b) one or more neutralizing antibodies binds an epitope in an influenza B Yamagata lineage or Victoria lineage viral strain.

74. The method of claim 62, wherein the neutralizing antibody is PY102, 6F12, CR6261, C179, CR8020, CR8043, CR8033, CR8071, F10, FI6, a FI6 variant, CR9114, 81.39, or any combinations thereof.

75. The method of claim 60, wherein the neutralizing antibody neutralizes a respiratory syncytial virus (RSV) subgroup A or subgroup B virus.

76. The method of claim 75, wherein the neutralizing antibody binds an epitope in the RSV attachment protein (G) or fusion protein (F).

77. The method of claim 75, wherein the neutralizing antibody binds an epitope in the RSV F protein, and wherein the neutralizing antibody neutralizes both RSV subgroup A and RSV subgroup B viruses.

78. The method of claim 75, wherein the neutralizing antibody binds an epitope in antigenic region I, II, IV, or 0 of the RSV F protein.

79. The method of claim 75, wherein the neutralizing antibody is 54G10, MAbl9, 1308F, chlOlF, 5C4, D25, MPE8, AM14, AM16, AM23, palivizumab, motavizumab, or any combinations thereof.

80. The method of claim 60, wherein the neutralizing antibody neutralizes a human metapneumovirus (hMPV) subgroup Al, A2, Bl, or B2 virus.

81. The method of claim 80, wherein the neutralizing antibody binds an epitope in the hMPV attachment protein (G) or fusion protein (F).

82. The method of claim 80, wherein the neutralizing antibody binds an epitope in the hMPV F protein, and wherein the neutralizing antibody neutralizes subgroup Al, A2, Bl and B2 hMPV viruses.

83. The method of claim 80, wherein the neutralizing antibody binds an epitope in epitope groups 2, 3, 4, 5, and 6 of the hMPV F protein.

84. The method of claim 80, wherein the neutralizing antibody is 54G10, DS7, MAb 338, MAb 234, MAb 628, or any combinations thereof.

85. The method of claim 60, wherein the neutralizing antibody binds an epitope in a

Pneumovirinae family virus F protein and neutralizes both RSV and hMPV.

86. The method of claim 85, wherein the neutralizing antibody is 54G10 or MPE8.

87. The method of claim 60, wherein the neutralizing antibody binds an epitope in a GII.4 genotype norovirus.

88. The method of claim 87, wherein the neutralizing antibody binds an epitope in the major capsid protein of a GII.4 norovirus.

89. The method of claim 88, wherein the neutralizing antibody binds an epitope in the P domain of the major capsid protein of a GII.4 norovirus.

90. The method of claim 89, wherein the neutralizing antibody is NVB 71.4 or

GII.4.2002. G5.

91. A method of reducing the likelihood or severity of an allergic reaction in an individual comprising: applying an anti -allergic composition to the surface of the individual’s skin, wherein the anti -allergic composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable for topical application, wherein the anti allergic composition reduces the risk of an allergic reaction upon exposure to an allergen or environmental contaminant.

92. A method of reducing the likelihood or severity of an allergic reaction in an individual comprising: applying an anti -allergic composition to the surface of a solid object, wherein the anti-allergic composition comprises an effective amount of a neutralizing antibody and a pharmaceutically acceptable carrier or excipient suitable, wherein the anti -allergic composition reduces the risk of an allergic reaction upon exposure to an allergen or environmental contaminant.

93. The method of claim 91 or 92, wherein the anti-allergic composition comprises a mixture of two or more neutralizing antibodies.

94. The method of claim 91, wherein the anti -allergic composition is applied to the individual’s hands, arms, legs, feet, torso, or face.

95. The method of claim 92, wherein the anti -allergic composition is applied to an article of clothing.

96. The method of claim 91 or 92, wherein the anti-allergic composition is formulated as a aqueous or non-aqueous solution or liquid, spray, aerosol, gel, powder, emulsion, suspension, lotions, cream, ointment, foam, oil, liposome, nanoparticle, paste, or stick.

97. The method of claim 91 or 92, wherein the allergic reaction is caused by a Toxicodendron species of plant, an alkylresorcinol, neomycin, or an environmental contaminant.

98. The method of claim 97, wherein the environmental contaminant is nickel, gold, or chromium.

99. The method of claim 91 or 92, wherein the anti-allergic composition comprises an anti- urushiol antibody.