Differential antiviral immune response in swine model of influenza vaccine-associated enhanced respiratory disease. (VIR2P.1026)

Abstract

Abstract Genetic drift and introduction of human seasonal influenza A virus (IAV) have resulted in six H1 phylogenetic clusters in swine. In humans reports suggest that prior vaccination against seasonal IAV (pre-2009) may result in enhanced disease following infection with pandemic 2009 IAV (pH1N1). Similarly, vaccine-associated enhanced respiratory disease (VAERD) has been reported in pigs that were vaccinated with one antigenic H1 subtype (human-like H1δ1) and subsequently challenged with pH1N1. To investigate the immune response associated with VAERD to delineate a mechanism for enhanced disease pigs were vaccinated with adjuvanted, inactivated H1δ1 and subsequently challenged with pH1N1 (Vx/Ch). Non-vaccinated (NV)/Ch and NV/non-challenged (NC) were included. Vaccination elicited IAV-specific IgG that cross-reacted with pH1N1 but did not neutralize infectivity. Proinflammatory cytokines IL-8, IL-1β and IL-6 were significantly elevated in lungs of Vx/Ch pigs compared to NV/Ch pigs. However, IFNα levels were significantly lower in lungs of Vx/Ch pigs compared to NV/Ch pigs indicating a difference in activation of antiviral immune pathway(s). IFNα mRNA levels were the same in tracheal epithelial cells collected from Vx/Ch and NV/Ch pigs; however, IFNα mRNA levels in alveolar macrophages (AM) from NV/Ch pigs were significantly increased over Vx/Ch pigs. We hypothesize vaccine-potentiated immunopathology through dysregulation of AM innate responses potentiates disease.