Location: Virus and Prion ResearchTitle: Enhanced Pneumonia and Proinflammatory Cytokine Response in Pigs Challenged with Pandemic 2009 A/H1N1 Influenza Virus Following Vaccination with an Inactivated delta-Cluster H1N2 Virus Author
Submitted to: Proceedings of the International Conference on Emerging Infectious Diseases
Publication Type: Abstract Only
Publication Acceptance Date: 6/5/2010
Publication Date: 7/14/2010
Citation: Gauger, P.C., Vincent, A.L., Loving, C.L., Lager, K.M., Janke, B.A., Roth, J.A. 2010. Enhanced pneumonia and proinflammatory cytokine response in pigs challenged with pandemic 2009 A/H1N1 influenza virus following vaccination with an inactivated delta-cluster H1N2 virus [abstract]. International Conference on Emerging Infectious Diseases. Paper No. L1345. Interpretive Summary:
Technical Abstract: Endemic strains of swine influenza A virus (IAV) in North America consist of the subtypes H1N1, H1N2, and H3N2. These circulating strains contain the triple reassortant internal gene (TRIG) cassette resulting from incorporation of genes from swine, avian, and human IAV’s. Genetic drift and reassortment have resulted in four H1 phylogenetic clusters designated as alpha, beta, gamma and delta and all currently co-circulate in US swine. Inactivated IAV vaccines do not provide adequate protection to heterologous homosubtypic IAV, nor heterosubtypic IAV. With the continued emergence of unique antigenic subtypes the need for an effective IAV vaccine in pigs remains high. Recent reports in the human population suggest that vaccination to IAV may result in enhanced disease following infection with the pandemic 2009 IAV (pH1N1). In a study with pigs, we vaccinated pigs with an inactivated delta-cluster H1N2 virus representative of the currently circulating delta-cluster strain of IAV in pigs. The HA gene is similar to that of the A/Brisbane/07 IAV contained in the most recent human seasonal vaccine. Three-weeks following the vaccine-boost, pigs were challenged with pH1N1 to evaluate protection (Vx/Ch group). A non-vaccinated/challenge group was included for controls (NV/Ch). Vaccinated pigs exhibited enhanced clinical signs of disease (fever, p<0.05) and macroscopic pneumonia scores (p<0.001) on day 5 following challenge. Interestingly, virus levels in the lung on day 5 were significantly lower in the Vx/Ch compared to the NV/Ch groups whereas levels of the proinflammatory cytokines IL-8, IL-1beta and IL-6 were significantly elevated in the lungs of Vx/Ch pigs compared to NV/Ch pigs. HI titers in the Vx group developed to the delta-cluster virus, but there was no cross-reactivity to the pH1N1 virus. Overall, this study demonstrates an enhancement of pneumonia in vaccinated pigs when infected with a heterologous, homosubtypic IAV (pH1N1). Although virus levels were not significantly higher in the lungs of Vx/Ch pigs compared to NV/Ch pigs, the levels of proinflammatory cytokines were significantly increased. We hypothesize a vaccine-potentiated immunopathology as the cause of the enhanced lesions and further work is being completed to address the mechanism.