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Title:   Author  item
                                            GORRES, J. PATRICK - National Institutes Of Health (NIH)item
                                            Lager, Kellyitem
                                            KONG, WING-PUI - National Institutes Of Health (NIH)item
                                            ROYALS, MICHAEL - Pharmajetitem
                                            TODD, J - National Institutes Of Health (NIH)item
                                            Baker, Amyitem
                                            WEI, CHIH-JEN - National Institutes Of Health (NIH)item
                                            Loving, Crystalitem
                                            ZANELLA, ERALDO - Universidad De Passo Fundoitem
                                            JANKE, BRUCE - Iowa State Universityitem
                                            Kehrli Jr, Marcusitem
                                            NABEL, GARY - National Institutes Of Health (NIH)item
                                            RAO, SRINIVAS - National Institutes Of Health (NIH)
  Submitted to: Clinical and Vaccine Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 9/7/2011
                                    Publication  Date: 11/1/2011
                                    Citation: Gorres, J.P., Lager, K.M., Kong, W.P., Royals, M., Todd, J.P., Vincent, A.L., Wei, C.J., Loving, C.L., Zanella, E.L., Janke, B., Kehrli, Jr., M.E., Nabel, G.J., Rao, S.S. 2011. DNA vaccination elicits protective immune responses against pandemic and classic swine influenza viruses in pigs. Clinical and Vaccine Immunology. 18(11):1987-1995.Interpretive Summary: Pandemic influenza (H1N1) 2009 virus has infected people in over 200 countries and also spread to animal species such as pigs. Development of better vaccines against influenza that are effective in multiple species would mitigate the impact of an emerging influenza virus. Here we report on the generation and testing of the safety and efficacy of DNA vaccines to protect against both classical swine influenza and the pandemic H1N1 strain in a pig challenge model.  We found that DNA vaccination (by a monovalent or trivalent vaccine) elicits robust serum antibody and cellular immune responses after three immunizations and confers significant protection against influenza challenge. Needle-free delivery of the vaccines exhibited efficacy that was comparable to conventional injection.  DNA vaccines are a promising alternative to traditional vaccines, since they can potentially induce broad-based protection with more efficient production methods. In this study, we evaluated monovalent and trivalent DNA vaccine constructs in eliciting both humoral and cellular immune responses and in protecting pigs against viral shedding and lung pathology after challenge with pandemic H1N1 or classic swine H1N1 influenza virus.  With the monovalent H1N1 DNA vaccine, we observed robust antibody responses against both the 2009 pandemic A/H1N1 virus and a swine influenza virus A/Ohio/2007.  We also observed protection against H3N1 SIV challenge in pigs vaccinated with the trivalent vaccine that contained both H1N1 viruses tested and a swine H3N2 isolate. By reducing and clearing influenza virus earlier in the infection period and preventing viral replication in the lung, DNA vaccination may prevent the development of clinical pathology, the spread of disease to other animals or humans, and the formation of novel virulent strains. However, while the protection of experimental pigs against classical swine and pandemic influenza is promising, more effort will be required to develop DNA vaccines into a viable and practical alternative to traditional vaccination strategies.
                                Technical Abstract: Swine influenza is a highly contagious viral infection in pigs that significantly impacts the pork industry due to weight loss and secondary infections. There is also the potential of a significant public health threat, highlighted by the possibility that the 2009 H1N1 pandemic strain emerged from reassortment events between avian, swine, and human influenza within pigs. As classic and pandemic H1N1 strains continue to circulate, an effective vaccine may be the best strategy to protect the pork industry and public health. Current inactivated vaccines available for swine influenza protect only against viral strains closely related to the vaccine strain, and egg-based production of these vaccines is insufficient to respond to large outbreaks. DNA vaccines are a promising alternative, since they can potentially induce broad-based protection with more efficient production methods. In this study, we evaluated monovalent and trivalent DNA vaccine constructs in eliciting both humoral and cellular immune responses, and protecting pigs against viral shedding and lung pathology after challenge with pandemic H1N1 or classic swine H1N1 influenza virus. We also compared the protective efficacy of a needle-free delivery method to conventional needle/syringe injection. We report that DNA vaccination elicits robust serum antibody and cellular responses after three immunizations, and confers significant protection against influenza challenge. Needle-free delivery exhibited efficacy that was comparable to conventional injection, and should be considered for development as a practical alternative for vaccine administration.


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