Seasonal FluMist Vaccination Induces Cross-Reactive T Cell Immunity against H1N1 (2009) Influenza and Secondary Bacterial Infections

Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
The Journal of Immunology (Impact Factor: 4.92). 01/2011; 186(2):987-93. DOI: 10.4049/jimmunol.1002664
Source: PubMed


T cell epitopes have been found to be shared by circulating, seasonal influenza virus strains and the novel pandemic H1N1 influenza infection, but the ability of these common epitopes to provide cross-protection is unknown. We have now directly tested this by examining the ability of live seasonal influenza vaccine (FluMist) to mediate protection against swine-origin H1N1 influenza virus infection. Naive mice demonstrated considerable susceptibility to H1N1 Cal/04/09 infection, whereas FluMist-vaccinated mice had markedly decreased morbidity and mortality. In vivo depletion of CD4(+) or CD8(+) immune cells after vaccination indicated that protective immunity was primarily dependent upon FluMist-induced CD4(+) cells but not CD8(+) T cells. Passive protection studies revealed little role for serum or mucosal Abs in cross-protection. Although H1N1 influenza infection of naive mice induced intensive phagocyte recruitment, pulmonary innate defense against secondary pneumococcal infection was severely suppressed. This increased susceptibility to bacterial infection was correlated with augmented IFN-γ production produced during the recovery stage of H1N1 influenza infection, which was completely suppressed in mice previously immunized with FluMist. Furthermore, susceptibility to secondary bacterial infection was decreased in the absence of type II, but not type I, IFN signaling. Thus, seasonal FluMist treatment not only promoted resistance to pandemic H1N1 influenza infection but also restored innate immunity against complicating secondary bacterial infections.

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Available from: Dennis Metzger, Feb 11, 2015
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    • "Cellular immunity at the mucosal surface has been shown in the regulation of effector immune cell functions where CD8 + T-cell response to live attenuated vaccines are thought to contribute significantly to crossprotection against various influenza strains (Sun et al., 2011). On the contrary, effector cell functions of CD8+ T-cells have also failed to induce protection against shigellosis (Jehl et al., 2011). "
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    • "In this context, there is experimental evidence on NP-based vaccines which promote CD4+ T cell responses contributing towards protective immunity [22], [66]. This phenomenon is not restricted only to influenza, since numerous infectious models have demonstrated the importance of CD4+ T cells in cellular mediated protection [67], [68]. "
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    • "In parallel with global efforts to develop CAIVs against the pdmH1N1,39,40,60,61 many researchers also evaluated the cross-reactivity between the seasonal CAIVs and the pdmH1N1, with the hope that the seasonal CAIVs that contained H1N1 subtype would elicit protection against the pdmH1N1. The comparative studies with seasonal CAIVs and inactivated vaccines revealed the superior protection against pdmH1N1 by the seasonal CAIVs, and the cross-reactive CTL responses were proposed to be the most likely correlates for this protection.38,62,63 Of note, in humans with prior exposure to the pdmH1N1 or immunized with inactivated H1N1 vaccine, broadly cross-reactive antibodies dominated the human B cell responses against heterologous influenza strains,64,65 suggesting that the HA of the pdmH1N1 might carry many conserved epitopes and was able to preferentially elicit antibodies specific to those epitopes. "
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