Abstract
Influenza A viruses (IAV) of subtypes H1N1, H1N2, and H3N2 are endemic in US domestic swine populations and contribute to significant economic losses annually and pose a persistent pandemic threat. Adjuvanted, whole-inactivated virus (WIV) vaccines are the primary countermeasure to control IAV in swine. The compositions of these vaccines are matched for hemagglutinin (HA) strain and content, often ignoring the other IAV glycoprotein, the neuraminidase (NA). The IAV NA is immunogenic and antibodies targeting epitopes adjacent to the active site have been shown to inhibit the sialidase activity of NA thereby reducing virus replication and shedding. To assess the ability of neuraminidase inhibiting (NAI) antibodies induced from WIV administration to protect swine from challenge with IAV containing homologous and heterologous NA, we produced WIV composed of viruses with an irrelevant mismatched H9 HA but expressing NA proteins from two predominant clades (N2-2002A.2 and N22002B.2) currently circulating in US domestic swine populations. Pigs that received two doses of H9N2 WIV developed vaccine-specific neuraminidase inhibition antibodies and when challenged with a wild-type H3N2 virus containing homologous NA, displayed reduced virus shedding in the upper respiratory tract and decreased virus titers in the lung compared to unvaccinated controls. Pigs challenged with H3N2 containing a heterologous NA also had reduced virus titers in the nasal swab and BALF samples. Together these results show that NAI antibodies cross-protected across phylogenetic clades and reduced virus replication and shedding in swine.