Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection following Intranasal Influenza A Virus Vaccination in Pigs.
In North American swine, there are numerous antigenically distinct H1 influenza A virus (IAV) variants currently circulating, making vaccine development difficult due to the inability to formulate a vaccine that provides broad cross-protection. Experimentally, live-attenuated influenza virus (LAIV) vaccines demonstrate increased cross-protection compared to inactivated vaccines. However, there is no standardized assay to predict cross-protection following LAIV vaccination. Hemagglutination-inhibiting (HI) antibody in serum is the gold standard correlate of protection following IAV vaccination. LAIV vaccination does not induce a robust serum HI antibody titer; however, a local mucosal antibody response is elicited. Thus, a live-animal sample source that could be used to evaluate LAIV immunogenicity and cross-protection is needed. Here, we evaluated the use of oral fluids (OF) and nasal wash (NW) collected after IAV inoculation as a live-animal sample source in an enzyme-linked immunosorbent assay (ELISA) to predict cross-protection in comparison to traditional serology. Both live-virus exposure and LAIV vaccination provided heterologous protection, though protection was greatest against more closely phylogenetically related viruses. IAV-specific IgA was detected in NW and OF samples and was cross-reactive to representative IAV from each H1 cluster. Endpoint titers of cross-reactive IgA in OF from pigs exposed to live virus was associated with heterologous protection. While LAIV vaccination provided significant protection, LAIV immunogenicity was reduced compared to live-virus exposure. These data suggest that OF from pigs inoculated with wild-type IAV, with surface genes that match the LAIV seed strain, could be used in an ELISA to assess cross-protection and the antigenic relatedness of circulating and emerging IAV in swine.
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA.
Holly R
HR
Hughes
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA.
Amy L
AL
Vincent
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA.
Susan L
SL
Brockmeier
Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, Iowa, USA.
Phillip C
PC
Gauger
Department of Veterinary Medicine, University of Maryland, College Park, College Park, Maryland, USA.
Lindomar
L
Pena
Department of Veterinary Medicine, University of Maryland, College Park, College Park, Maryland, USA.
Jefferson
J
Santos
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA.
Douglas R
DR
Braucher
Department of Veterinary Medicine, University of Maryland, College Park, College Park, Maryland, USA.
Daniel R
http://orcid.org/0000-0002-6569-5689
DR
Perez
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA crystal.loving@ars.usda.gov.
Crystal L
CL
Loving
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D056738:Cross Protection; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006385:Hemagglutination Inhibition Tests; D007070:Immunoglobulin A / Q000096:biosynthesis; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D009055:Mouth / Q000276:immunology* / Q000821:virology; D017817:Nasal Lavage Fluid / Q000276:immunology* / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D013552:Swine; D013553:Swine Diseases / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated