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Title: The molecular determinants of antibody recognition and antigenic drift in the H3 hemagglutinin of swine influenza A virus

item ABENTE, EUGENIO - Oak Ridge Institute For Science And Education (ORISE)
item SANTOS, JEFFERSON - University Of Georgia
item LEWIS, NICOLA - University Of Cambridge
item GAUGER, PHILLIP - Iowa State University
item Stratton, Jered
item SKEPNER, EUGENE - University Of Cambridge
item Anderson, Tavis
item RAJAO, DANIELA - Non ARS Employee
item PEREZ, DANIEL - University Of Georgia
item Baker, Amy

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/28/2016
Publication Date: 8/26/2016
Citation: Abente, E.J., Santos, J., Lewis, N.S., Gauger, P.C., Stratton, J., Skepner, E., Anderson, T.K., Rajao, D.S., Perez, D.R., Vincent, A.L. 2016. The molecular determinants of antibody recognition and antigenic drift in the H3 hemagglutinin of swine influenza A virus. Journal of Virology. 90(18):8266-8280.

Interpretive Summary: Swine influenza virus is an important pathogen in swine that can cause significant economic losses for swine producers. Use of efficacious vaccines can reduce the burden of disease and minimize clinical symptoms caused by the virus. Swine viruses circulating in the United States continuously evolve and commercial vaccines may be less effective at providing protection. The hemagglutinin (HA) protein of influenza A virus is the most important target of the immune system. Small changes were made to the HA protein of an H3N2 swine virus, and we showed that specific sites play an important role in immunity and potentially in vaccine protection. Defining these sites and testing their effects in pigs will improve vaccine strain selection and allow for rapid detection of emerging antigenic variants.

Technical Abstract: Influenza A virus (IAV) of the H3 subtype is an important pathogen that affects both humans and swine. The main intervention strategy for preventing infection is vaccination to induce neutralizing antibodies against the surface glycoprotein hemagglutinin (HA). However, due to antigenic drift, vaccine components must be periodically updated. The antigenic evolution of the human H3 HA was mapped to substitutions occurring at 7 positions in the HA1 region. Six of the same 7 positions were indicated in swine H3 antigenic evolution. To experimentally test the effect on antigenicity of these 7 positions, substitutions were introduced into the HA of an isogenic swine-lineage virus. Antigenic cartography using hemagglutination inhibition (HI) data with monovalent swine antisera was used to characterize the antigenic phenotype of virus mutants. Combinations of substitutions within the antigenic motif (positions 145, 155, 156, 158, 159, 189, 193) caused significant changes in antigenicity. One virus mutant that varied at only two positions relative to wild type had a >4-fold reduction in HI titers compared to homologous antisera. Potential changes in pathogenesis and transmission were evaluated in the double mutant in a pathogenesis and transmissibility study in pigs. Although the double mutant had comparable virus shedding titers and transmissibility, it caused significantly lower percentage of lung lesions. Elucidating the antigenic effects of specific amino acid substitutions at these sites in swine H3 IAV have important implications for understanding IAV virus evolution in populations with immune pressure as well as for improved vaccine development and control strategies in swine.