Live attenuated influenza A virus vaccine expressing an IgA-inducing protein protects pigs against replication and transmission.

Authors: RAJOA, DANIELA - University Of Georgia; ZANELLA, GIOVANA - Iowa State University; BRAND, MEGHAN - Orise Fellow; KHAN, SHEHROZ - University Of Georgia; MILLER, MICHAEL - University Of Georgia; FERRERI, LUCAS - University Of Georgia; CACERES, C. JOAQUIN - University Of Georgia; CADERNAS-GARCIA, STIVALIS - University Of Georgia; SOUZA, CARINE - Orise Fellow; Anderson, Tavis; GAUGER, PHILLIP - Iowa State University; Baker, Amy; PEREZ, DANIEL - University Of Georgia

Submitted to: Frontiers in Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2023
Publication Date: 2/14/2023
Citation: Rajoa, D.S., Zanella, G.C., Brand, M.W., Khan, S., Miller, M.E., Ferreri, L.M., Caceres, C., Cadernas-Garcia, S., Souza, C.K., Anderson, T.K., Gauger, P.C., Baker, A.L., Perez, D.R. 2023. Live attenuated influenza A virus vaccine expressing an IgA-inducing protein protects pigs against replication and transmission.. Frontiers in Virology. 3. Article 1042724. https://doi.org/10.3389/fviro.2023.1042724.
DOI: https://doi.org/10.3389/fviro.2023.1042724

Interpretive Summary: Influenza A virus is a major respiratory pathogen in swine that leads to significant economic loss in the swine industry, and there is a critical need to improve commercial vaccines. Traditional vaccines use killed virus and are given by injection into the muscle. These vaccines work well for similar viruses, but lose effectiveness against infection with a dissimilar influenza virus. Live attenuated influenza vaccines (LAIV) that are weakened by genetic changes offer multiple advantages over traditional vaccines for swine by stimulating immunity in the respiratory tract and improving protection against dissimilar viruses. In this work we demonstrated an LAIV designed to include a protein to stimulate immunity worked equally as well as the precursor LAIV without the immunostimulatory protein and reduced shedding and spread of IAV. Such improvement of IAV vaccines will reduce influenza disease and economic loss in commercial swine and reduce the risk of influenza transmission to people.

Technical Abstract: The rapid evolution of influenza A viruses (IAV) complicates the disease control for animal and public health. Although vaccination is an effective way to control influenza, available vaccines for use in swine result in limited protection against the antigenically distinct IAV that currently co-circulate in pigs. Vaccines administered parenterally usually stimulate IgG antibodies but not a strong mucosal IgA response, which is typically more cross-reactive. We developed a live attenuated influenza virus (LAIV) vaccine containing IgA-inducing protein (IGIP) as an adjuvant to enhance the mucosal IgA response against influenza. This Flu-IGIP vaccine was tested in a bivalent formulation (H1N1 and H3N2) against challenge with antigenically drifted viruses in pigs. Pigs were vaccinated intranasally with either a bivalent Flu-IGIP or a bivalent Flu-att (control without IGIP) and boosted two weeks later. Three weeks post boost, pigs were challenged with antigenically drifted H1N1 or H3N2 virus. Vaccinated pigs had increased numbers of influenza-specific IgA-secreting cells in PBMC two weeks post boost and higher numbers of total and influenza-specific IgA-secreting cells in bronchoalveolar lavage fluid (BALF) 5 days post infection (dpi) compared to naïve pigs. Pigs vaccinated with both Flu-IGIP and Flu-att shed significantly less virus after H1N1 or H3N2 challenge compared to non-vaccinated pigs. Vaccination with Flu-att reduced respiratory transmission, while Flu-IGIP fully blocked transmission regardless of challenge virus. Both Flu-IGIP and Flu-att vaccines reduced virus replication in the lungs and lung lesions after challenge with either virus. IgG and IgA levels in BALF and nasal wash of vaccinated pigs were boosted after challenge as soon as 5 dpi and remained high at 14 dpi. Our results indicate that Flu-IGIP has the potential to upregulate protective IgA responses leading to protection from clinical signs, replication and shedding after antigenically drifted influenza virus infection.