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Title:   Author  item
                                            GAUGER, PHILLIP - Iowa State Universityitem
                                            Loving, Crystalitem
                                            Lager, Kellyitem
                                            JANKE, BRUCE - Iowa State Universityitem
                                            Kehrli Jr, Marcusitem
                                            ROTH, JAMES - Iowa State Universityitem
                                            Baker, Amy
  Submitted to: Viral Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 5/25/2013
                                    Publication  Date: 10/1/2013
                                    Citation: Gauger, P.C., Loving, C.L., Lager, K.M., Janke, B.H., Kehrli, Jr., M.E., Roth, J.A., Vincent, A.L. 2013. Vaccine-associated enhanced respiratory disease does not interfere with the adaptive immune response following challenge with pandemic A/H1N1 2009. Viral Immunology. 26(5):314-321.Interpretive Summary: The implication of being infected with influenza A viruses (IAV) that do not match the virus contained in vaccines is a concern for mammals in which vaccine is routinely used, including humans and pigs. We have previously described an aggravated pneumonia, termed vaccine associated enhanced respiratory disease (VAERD), induced when the IAV strain in the vaccine is of the same HA subtype as the challenge virus, but differs enough that the vaccine no longer induces protective antibody immunity. This study investigated if VAERD would interfere with the subsequent immune response against the heterologous challenge virus inciting the VAERD. Pigs vaccinated with an inactivated swine H1N2 (MN08) vaccine similar to pre-2009 seasonal human viruses and challenged with heterologous A(H1N1) pandemic 2009 (H1N1pdm09) were analyzed for adaptive immune responses after the challenge. Vaccinated pigs demonstrated a robust humoral immune response and elevated local adaptive cytokine levels, indicating VAERD does not adversely affect the induction of an immune response against subsequent heterologous challenge despite the dramatic lung damage caused by VAERD. Further work is required to understand the VAERD phenomenon and downstream consequences following the VAERD insult to the lungs. This study provides data for better influenza vaccine selection by those in the animal and human health fields as well as vaccine manufacturers.
                                Technical Abstract: Background. The implications of sequential prime and challenge with mismatched influenza A viruses is a concern in mammals including humans. We evaluated the ability of pigs affected with vaccine associated enhanced respiratory disease (VAERD) to generate a humoral immune response against the heterologous challenge virus inciting the VAERD.
Methods. Pigs vaccinated with an inactivated swine delta-cluster H1N2 (MN08) and challenged with heterologous A(H1N1) pandemic 2009 (H1N1pdm09) were analyzed for adaptive immune responses. 
Results. Vaccinated pigs demonstrated significantly higher post-challenge anti- H1N1pdm09 serum neutralizing antibodies by 14 days post infection (dpi) and significantly higher serum and lung anti-H1N1pdm09 IgG antibodies compared to challenge only pigs. Lung IgA antibodies to either antigen were detected at 2, 5 and 21 dpi in vaccine primed pigs contrasting against the delayed mucosal IgG and IgA antibody responses detected in the non-vaccinated challenged group at 21 dpi. Cross-reactive anti-MN08 hemagglutination inhibition antibodies were not detected in the challenge only pigs.
Conclusion. Vaccine primed pigs demonstrated a robust humoral immune response and elevated local adaptive cytokine concentrations, indicating VAERD does not adversely affect the induction of an immune response against heterologous challenge. In addition, original antigenic sin does not appear to be a component of VAERD.


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