Neuraminidase inhibiting antibody responses in pigs differ between influenza A virus N2 lineages and by vaccine type

Authors: SANDBULTE, MATTHEW - Iowa State University; GAUGER, PHILLIP - Iowa State University; KITIKOON, PRAVINA - Former ARS Employee; CHEN, HONGJUN - University Of Maryland; PEREZ, DANIEL - University Of Maryland; ROTH, JAMES - Iowa State University; Baker, Amy

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2016
Publication Date: 7/19/2016
Publication URL: https://handle.nal.usda.gov/10113/62846
Citation: Sandbulte, M.R., Gauger, P.C., Kitikoon, P., Chen, H., Perez, D.P., Roth, J.A., Vincent, A.L. 2016. Neuraminidase inhibiting antibody responses in pigs differ between influenza A virus N2 lineages and by vaccine type. Vaccine. 34(33):3773-3779.

Interpretive Summary: Influenza A virus (IAV) is an important respiratory pathogen in pigs as well as humans. Neuraminidase (NA) proteins of IAVs are located on the surface of the virus and constitute the "N" subtype based on NA gene variation. Host antibodies against NA can reduce viral replication and limit disease severity and the NA gene evolves to avoid host immunity. However, NA antibodies are not routinely measured, especially in pigs. This manuscript describes the NA antibody profiles using an NA inhibition (NI) assay in piglets vaccinated with intramuscular whole-inactivated virus, intranasal live-attenuated influenza virus, and intranasal wild type IAV. Additional sera were from pigs vaccinated in presence of passive maternally-derived antibodies to evaluate maternal antibody interference in the NI antibody response to vaccines. We showed that the vaccines tested induced strong NA antibody responses in serum and respiratory tract. Additionally, viruses containing NA genes of different genotypes within the N2 serotype caused reduced NI cross-reactivity. Swine IAV vaccines that induce robust NI responses are likely to provide broader protection against the diverse and rapidly evolving IAV strains that circulate in pig populations and specificity to NA genotype is likely required for optimal vaccine efficacy.

Technical Abstract: The neuraminidase (NA) protein of influenza A viruses (IAV) has important functional roles in the viral replication cycle. Antibodies specific to NA can reduce viral replication and limit disease severity, but are not routinely measured. We analyzed NA inhibiting (NI) antibody titers in serum and respiratory specimens of pigs vaccinated with intramuscular whole-inactivated virus (WIV), intranasal live-attenuated influenza virus (LAIV), and intranasal wild type (WT) IAV. NI titers were also analyzed in sera from an investigation of piglet vaccination in the presence of passive maternally-derived antibodies. Test antigens contained genetically divergent swine-lineage NA genes homologous or heterologous to the vaccines with mismatched hemagglutinin genes (HA). Naïve piglets responded to WIV and LAIV vaccines and WT infection with strong homologous serum NI titers. Cross-reactivity to heterologous NAs depended on the degree of genetic divergence between the NA genes. Bronchoalveolar lavage specimens of LAIV and WT-immunized groups also had significant NI titers against the homologous antigen whereas the WIV group did not. Piglets of vaccinated sows received high levels of passive NI antibody, but their NI responses to homologous LAIV vaccination were impeded. These data demonstrate the utility of the enzyme-linked lectin assay for efficient NI antibody titration of serum as well as respiratory tract secretions. Swine IAV vaccines that induce robust NI responses are likely to provide broader protection against the diverse and rapidly evolving IAV strains that circulate in pig populations. Mucosal antibodies to NA may be one of the protective immune mechanisms induced by LAIV vaccines.