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Title:   Author  item
                                            RAJÃO, DANIELA - Non ARS Employeeitem
                                            Loving, Crystalitem
                                            GAUGER, PHILLIP - Iowa State Universityitem
                                            KITIKOON, PRAVINA - Non ARS Employeeitem
                                            Baker, Amy
  Submitted to: Vaccine
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/17/2014
                                    Publication  Date: 7/29/2014
                                    Citation: Rajão, D.S., Loving, C.L., Gauger, P.C., Kitikoon, P., Vincent, A.L. 2014. Influenza A virus hemagglutinin protein subunit vaccine elicits vaccine-associated enhanced respiratory disease. Vaccine. 32(40):5170-5176.Interpretive Summary: Influenza, caused by influenza A viruses (IAV), is one of the most prevalent respiratory diseases of swine. The combination of a wide variety of IAV circulating among swine in the United States with the extensive use of inactivated IAV vaccines creates potential conditions for the occurrence of vaccine-associated enhanced respiratory disease (VAERD). VAERD was previously shown to occur with whole inactivated virus vaccines, but subunit vaccines with individual IAV proteins had not been evaluated. A vaccine that contained the IAV surface protein hemagglutinin (HA) alone was shown to be sufficient to induce VAERD in this study. In contrast, a live attenuated influenza virus (LAIV) vaccine provided significant partial protection against the same heterologous challenge and did not result in disease enhancement. This information indicates that disease enhancement should be taken into account when evaluating vaccine efficacy to prevent such problems in field conditions, and that LAIV could be a better alternative than inactivated or subunit vaccines to improve vaccine efficacy and avoid VAERD.
                                Technical Abstract: Vaccine-associated enhanced respiratory disease (VAERD) can occur when pigs are challenged with heterologous virus in the presence of non-neutralizing but cross-reactive antibodies elicited by whole inactivated virus (WIV) vaccine. The aim of this study was to compare the effects of heterologous delta1-H1N2 influenza A virus (IAV) challenge after vaccination of pigs with 2009 pandemic H1N1 virus (H1N1pdm09) recombinant hemagglutinin (HA) subunit vaccine (HA-SV) or temperature-sensitive live attenuated influenza virus (LAIV) vaccine, and to assess the role of immunity to HA in the development of VAERD. Both HA-SV and LAIV vaccines induced high neutralizing antibodies to virus with homologous HA (H1N1pdm09), but not heterologous challenge virus (delta1-H1N2). LAIV partially protected pigs, resulting in reduced virus shedding and faster viral clearance, as no virus was detected in the lungs by 5 days post infection (dpi). HA-SV vaccinated pigs developed more severe lung and tracheal lesions consistent with VAERD following challenge. These results demonstrate that the immune response against the HA protein alone is sufficient to cause VAERD following heterologous challenge.


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