Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection following Intranasal Influenza A Virus Vaccination in Pigs

• Published in: Clinical and vaccine immunology Vol. 22; no. 10; pp. 1109 - 1120
• Main Authors: Hughes, Holly R, Vincent, Amy L, Brockmeier, Susan L, Gauger, Phillip C, Pena, Lindomar, Santos, Jefferson, Braucher, Douglas R, Perez, Daniel R, Loving, Crystal L
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.10.2015
• Subjects: Administration, Intranasal; Animals; Antibodies, Viral - blood; Cross Protection; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Hemagglutination Inhibition Tests; Immunoglobulin A - biosynthesis; Influenza A virus - classification; Influenza A virus - genetics; Influenza A virus - immunology; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - pathogenicity; Influenza A Virus, H3N2 Subtype - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Mouth - immunology; Mouth - virology; Nasal Lavage Fluid - immunology; Nasal Lavage Fluid - virology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - veterinary; Orthomyxoviridae Infections - virology; Swine; Swine Diseases - prevention & control; Vaccines; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology
• ISSN: 1556-6811; 1556-679X
• DOI: 10.1128/cvi.00358-15

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.