Evaluation of a nanoparticle influenza vaccine in the pig model

Influenza A virus (IAV) infection causes substantial disease burden and vaccines capable of conferring broad immunity are lacking, necessitating frequent reformulation of seasonal vaccines. The purpose of this study was to evaluate the immunogenicity and efficacy of an influenza nanoparticle vaccine developed to confer immunity against human seasonal H1N1 viruses from the pandemic 2009 (1A.3.3.2) clade and to compare this vaccine with a conventional, whole inactivated virus (WIV) vaccine. Using the pig model of human influenza, both vaccines were found to be immunogenic and elicited humoral and cellular immune responses that reflected the differences in vaccine design. Vaccine efficacy was evaluated by challenging vaccinated or unvaccinated, control pigs with a swine-origin 1A.3.3.2 virus and monitoring these groups longitudinally. Nasal shedding of viral RNA was reduced in the vaccinated groups compared to controls, although a statistically significant reduction was only observed on certain days in WIV-vaccinated pigs. To better understand correlates of immune protection, expression of porcine Mx1, CCL2 and TNFa mRNA was assessed in tissues. Virus infection of unvaccinated pigs induced mRNA expression of porcine Mx1, an innate IAV inhibitor protein, in lung tissue. In contrast, elevated Mx1 mRNA levels were not observed in lung tissue from WIV-vaccinated and, to a lesser extent, nanoparticle vaccinated pigs. These findings suggest that, although reduction in virus shedding was limited following challenge, vaccination elicited an immunoprotective response in the lower respiratory tract of challenged animals.