Immune mechanisms associated with enhanced influenza A virus disease versus cross-protection in vaccinated pigs. (VAC4P.1064)

Abstract

Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of cross-reactive, non-neutralizing antibody to the challenge IAV strain suggesting circulating immune complexes and/or antibody dependent cell-mediated cytotoxicity could contribute to pathology. Moreover, pathological findings in VAERD lungs include significant lymphocytic infiltration and increased levels of proinflammatory cytokines. In order to further delineate the immune mechanism associated with VAERD versus partial-protection we defined the lymphocyte populations infiltrating the lungs following challenge, as well as level of complement activation. Post-challenge, IAV-specific IFNγ secreting cells in the lungs were increased in pigs with VAERD compared to non-vaccinated, challenged controls. CD8 T cells and NK cells were significantly higher in the lungs of pigs protected from homologous challenge, suggesting these cells may play a role in protection. Interestingly, pigs with VAERD had a significant increase in memory T cells that was not observed in pigs without VAERD. Additionally, complement activation was significantly higher in the lungs of pigs experiencing VAERD. These data further describe the lymphocytic pathology associated with VAERD and suggest a role for complement activation in the development of VAERD disease pathology.