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Title:   Author  item
                                            Loving, Crystalitem
                                            Braucher, Douglasitem
                                            Brockmeier, Susanitem
                                            Baker, Amy
  Submitted to: Keystone Symposia
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 11/1/2012
                                    Publication  Date: 12/13/2012
                                    Citation: Loving, C.L., Braucher, D.R., Brockmeier, S.L., Vincent, A.L. 2012. Cross-reactive immune responses following vaccination with a live-attenuated influenza virus compared to adjuvanted, whole-inactivated virus in pigs. Immunological Mechanisms of Vaccination, Keystone Symposia. Paper No. 2038.Interpretive Summary:
                                Technical Abstract: Circulating influenza A virus (IAV) in North America pigs consist of H3N2, H1N2, and H1N1 (4 genetic clusters) which contain the triple reassortant internal gene (TRIG) cassette resulting from incorporation of genes from swine, avian, and human IAV. Adjuvanted, whole-inactivated virus (WIV) vaccines do not provide adequate protection and may even lead to vaccine associated enhanced respiratory disease (VAERD). However, live-attenuated influenza virus (LAIV) vaccines elicit more broadly protective responses and do not cause VAERD, though the mechanism of increased cross-protection has not been completely defined. Thus, we sought to compare responses following WIV or LAIV vaccination to homologous virus (pH1N1), homosubtypic, heterologous virus (gammaH1N1) and heterosubtypic virus (H3N2). The vaccine had pandemic HA and NA genes and a temperature-sensitive TRIG backbone. Hemagglutination inhibition (HI) antibody titers to pH1N1 were greater in WIV vaccinates compared to LAIV vaccinates; however, there was not a significant difference in serum neutralization (SN) titers. Both vaccine platforms induced SN antibody to gammaH1N1 and H3N2, though titers were much lower to H3N2 virus. Fifty-six days following vaccination, nasal wash (NW) and lung lavage were collected to evaluate antibody at the mucosal surfaces. While neutralizing antibody to pH1N1 virus was detected in both vaccine groups, only the pigs that received LAIV had cross-reactive neutralizing antibody to gammaH1N1 virus. In addition, LAIV vaccinates had NW IgA that cross-reacted with both the gammaH1N1 and H3N2 virus. While both vaccines induced the generation of IFN-gamma secreting cells (SC) in the periphery, numbers were highest to pH1N1 following LAIV vaccination. Both vaccines elicited similar numbers of IFN-gamma SCs cross-reactive to gammaH1N1 and H3N2 viruses. These data suggest that the greatest T cell responses are generated with an HA match between vaccine and challenge virus.


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