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Title:   Author  item
                                            KHURANA, SURENDER - Food And Drug Administration(FDA)item
                                            Loving, Crystalitem
                                            MANISCHEWITZ, JODY - Food And Drug Administration(FDA)item
                                            KING, LISA - Food And Drug Administration(FDA)item
                                            GAUGER, PHILLIP - Iowa State Universityitem
                                            HENNINGSON, JAMIE - Kansas State Universityitem
                                            Baker, Amyitem
                                            GOLDING, HANA - Food And Drug Administration(FDA)
  Submitted to: Science Translational Medicine
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/25/2013
                                    Publication  Date: 8/28/2013
                                    Citation: Khurana, S., Loving, C.L., Manischewitz, J., King, L.R., Gauger, P.C., Henningson, J., Vincent, A.L., Golding, H. 2013. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease. Science Translational Medicine. 5(200):200ra114.Interpretive Summary: Influenza A viruses cause pneumonia and respiratory disease in swine similar to that in humans and cause huge financial losses to pork producers. Use of whole inactivated influenza virus vaccines (WIV) in swine has increased over the past ten years in an effort to prevent disease and transmission of the virus. In this report, pigs administered a WIV followed by infection with the dissimilar 2009 pandemic human influenza A virus (pH1N1) demonstrated more severe clinical disease and lung lesions compared to non-vaccinated pigs infected with the same virus. Serum from the vaccinated pigs contained high levels of cross-reactive antibodies that bound to a conserved region of the pH1N1 virus hemagglutinin protein. These cross-reactive antibodies did not prevent virus infection, but instead enhanced pH1N1 infection, and this effect correlated with the lung damage in the pigs. This is the first study that suggests a major role for specific antibodies induced by vaccine in causing more severe disease after infection with influenza A virus and suggests caution in evaluating vaccines that may elicit such cross-reacting antibodies. These results are important to swine producers, veterinarians, scientists in the field, human public health officials, and vaccine manufacturers.
                                Technical Abstract: During the 2009 pandemic, several studies associated recent seasonal influenza vaccination with increased severity of clinical illness after pandemic H1N1 (pH1N1) infection. We developed a swine model to evaluate mismatched influenza vaccination associated enhanced respiratory disease (VAERD) following pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 virus vaccine (WIV-H1N2) enhanced pneumonia and disease following pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 antibodies that bound exclusively to the HA2 domain (aa 46-91) of the virus hemagglutinin. Cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of MDCK cells by promoting virus fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This is the first study that suggests a major role for fusion-enhancing anti-HA2 antibodies in VAERD, in absence of receptor-blocking antibodies.


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