A neuraminidase-based inactivated influenza virus vaccine significantly reduced virus replication and pathology following homologous challenge in swine

Authors: Kaplan, Bryan; SOUZA, CARINE - Iowa State University; KIMBLE, BRIAN - Oak Ridge Institute For Science And Education (ORISE); Wymore Brand, Meghan; Anderson, Tavis; GAUGER, PHILLIP - Iowa State University; PEREZ, DANIEL - University Of Georgia; Baker, Amy

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/26/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Influenza A viruses (IAV) continue to cause respiratory disease in US domestic swine populations contributing to significant economic losses annually as well as posing a persistent pandemic threat. Control of IAV in swine is challenging. Current vaccines are matched for hemagglutinin (HA) strain and content, though due to the high levels of variation observed in the HA, vaccine efficacy is reduced. To improve the efficacy of IAV vaccines for use in swine, an experimental vaccine targeting the neuraminidase (NA) protein was evaluated. Pigs that received two doses of a whole-inactivated virus (WIV) vaccine had a strong antibody response to the NA component of the vaccine. Subsequent infection with virus with a match NA showed that vaccinated pigs had lower levels of virus replication in the nasal cavities and lungs, as well as less lung pathology compared to unvaccinated controls. In some cases, the NA-based vaccine was able to provide protection against an IAV with a mismatched NA, showing these vaccines could provide broad protection. Together, the results from this study suggest that incorporating the NA protein into vaccines may improve influenza vaccine efficacy in swine.

Technical 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 N2-2002B.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.