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Title: Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (delta-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus

item GAUGER, PHILLIP - Iowa State University
item Baker, Amy
item Loving, Crystal
item Lager, Kelly
item JANKE, BRUCE - Iowa State University
item Kehrli Jr, Marcus
item ROTH, JAMES - Iowa State University

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/25/2011
Publication Date: 3/24/2011
Citation: Gauger, P.C., Vincent, A.L., Loving, C.L., Lager, K.M., Janke, B.H., Kehrli, Jr., M.E., Roth, J.A. 2011. Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (delta-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus. Vaccine. 29(15):2712-2719.

Interpretive Summary: Influenza A virus causes a respiratory disease in swine similar to that in humans. In addition, it is a component of the multiple pathogen porcine respiratory disease complex (PRDC) in growing pigs. Use of inactivated influenza virus vaccines in swine has increased over the past ten years in an effort to prevent disease and transmission of the virus. Inactivated vaccines work well when pigs are exposed to influenza viruses represented in the vaccine. However, vaccine efficacy is reduced when pigs are infected with new strains. In this report, pigs administered an inactivated influenza A vaccine followed by infection with the pandemic human influenza A virus (2009) demonstrated more severe clinical disease and lung lesions compared to non-vaccinated pigs inoculated with the same virus. Pigs vaccinated with the mismatched vaccine went off-feed, had elevated body temperatures, and increased coughing following infection compared to non-vaccinated pigs. Consistent with the signs of illness, vaccinated and challenged pigs had increased percentages of pneumonia and more lung damage compared to the non-vaccinated pigs. The antibody response in the vaccinated pigs did not block infection with the pandemic H1N1 virus in laboratory assays. This is a possible explanation for why the vaccine did not protect against infection in the pigs. These results indicate that vaccinating with an inactivated influenza virus may increase the severity of disease when pigs are exposed to a new strain of influenza virus compared to pigs that were not vaccinated. Active surveillance and monitoring of the quality of match between vaccine strains and strains infecting swine herds is necessary to prevent vaccine mismatch in the swine population. Future vaccines that stimulate improved immune responses across differing influenza viruses will be important to prevent infection and clinical disease and reduce the burden of this economically important disease. Since influenza viruses from swine may infect people, controlling influenza in the swine population has important implications to human health as well.

Technical Abstract: Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (delta-cluster) H1 six and three weeks before challenge with a H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies.