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Title:   Author  item
                                            SOUZA, CARINE - Universidade Federal Do Rio Grande Do Norteitem
                                            RAJÃO, DANIELA - Non ARS Employeeitem
                                            Loving, Crystalitem
                                            GAUGER, PHILLIP - Iowa State Universityitem
                                            PÉREZ, DANIEL - University Of Georgiaitem
                                            Baker, Amy
  Submitted to: Clinical and Vaccine Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 3/24/2016
                                    Publication  Date: 6/6/2016
                                    Citation: Souza, C.K., Rajão, D.S., Loving, C.L., Gauger, P.C., Pérez, D.R., Vincent, A.L. 2016. Age at vaccination and timing of infection do not alter vaccine-associated enhanced respiratory disease in influenza A virus infected pigs. Clinical and Vaccine Immunology. 23:470–482.Interpretive Summary: Whole inactivated virus (WIV) vaccines are widely used in the swine industry to reduce disease against influenza A virus (IAV) infection. 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). Here, we show that age of first vaccination or length of time between booster dose and subsequent challenge did not alter the development of VAERD in WIV vaccinated pigs. The length of time between booster dose and challenge did not negatively impact the positive outcome of the live attenuated influenza virus (LAIV) vaccine in direct comparison with WIV. Importantly, the mismatched component of a bivalent WIV did not override the protective effect of the matched vaccine component. This information indicates that disease enhancement should be taken into account when evaluating WIV vaccine efficacy under field conditions and that LAIV could be a better alternative than inactivated vaccines to improve vaccine efficacy and avoid VAERD.
                                Technical Abstract: Whole inactivated virus (WIV) vaccines are widely used in the swine industry to reduce clinical disease against homologous influenza A virus (IAV) infection. In pigs experimentally challenged with antigenically distinct heterologous IAV of the same hemagglutinin subtype, WIV vaccinates have been shown to develop vaccine-associated enhanced respiratory disease (VAERD). We evaluated the impact of vaccine valency, age at vaccination, and duration between vaccination and challenge on development of VAERD using vaccine containing delta1-H1N2 and challenge with pandemic H1N1 (pH1N1) virus. Pigs were vaccinated with monovalent WIV MN08 (delta1-H1N2) and bivalent (delta1-H1N2/H3N2) or (delta1-H1N2/pH1N1) vaccines then were challenged with pH1N1 at 3 weeks post-boost (wpb). Another group was vaccinated with the same monovalent WIV followed by challenge at 6 wpb to determine if time post-vaccination plays a role in development of VAERD. In a follow up study, the impact of age of first WIV vaccination (4 versus 9 weeks of age) with a boost three weeks later (7 versus 12 weeks of age) was evaluated. A monovalent live-attenuated influenza virus (LAIV) vaccine administered at 4 and 7 weeks of age was also included. All mismatched WIV groups had significantly higher lung lesions compared to LAIV, bivalent MN08-CA09 and controls groups. Age of first vaccination or length of time between booster dose and subsequent challenge did not alter the development of VAERD in WIV vaccinated pigs. Importantly, the mismatched component of the bivalent MN08-CA09 WIV did not override the protective effect of the matched vaccine component.


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