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

ABSTRACT 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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    • "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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    PLoS ONE 08/2014; 9(8):e104824. DOI:10.1371/journal.pone.0104824 · 3.23 Impact Factor
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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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    ABSTRACT: The desired effect of vaccination is to elicit protective immune responses against infection with pathogenic agents. An inactivated influenza vaccine is able to induce the neutralizing antibodies directed primarily against two surface antigens, hemagglutinin and neuraminidase. These two antigens undergo frequent antigenic drift and hence necessitate the annual update of a new vaccine strain. Besides the antigenic drift, the unpredictable emergence of the pandemic influenza strain, as seen in the 2009 pandemic H1N1, underscores the development of a new influenza vaccine that elicits broadly protective immunity against the diverse influenza strains. Cold-adapted live attenuated influenza vaccines (CAIVs) are advocated as a more appropriate strategy for cross-protection than inactivated vaccines and extensive studies have been conducted to address the issues in animal models. Here, we briefly describe experimental and clinical evidence for cross-protection by the CAIVs against antigenically distant strains and discuss possible explanations for cross-protective immune responses afforded by CAIVs. Potential barriers to the achievement of a universal influenza vaccine are also discussed, which will provide useful guidelines for future research on designing an ideal influenza vaccine with broad protection without causing pathogenic effects such as autoimmunity or attrition of protective immunity against homologous infection.
    Yonsei medical journal 03/2013; 54(2):271-82. DOI:10.3349/ymj.2013.54.2.271 · 1.29 Impact Factor
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    • "LAIVs are delivered into the nasal route and are capable of inducing mucosal secretory IgA antibodies , which are more cross-reactive against heterologous strains through their polymeric nature and higher avidity to viral antigens [15] [16]. Furthermore, besides inducing serum neutralizing antibodies against viral surface proteins, LAIVs activate T cell responses directed to a variety of epitopes generated from internal viral proteins during antigen processing [17] [18] [19]. The cold-adapted live attenuated donor strain X-31 ca was previously demonstrated to be not only productive in embryonated eggs but also highly immunogenic and provide solid protection against lethal challenges in mice [20]. "
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    ABSTRACT: The 2009 pandemic influenza H1N1 (pdmH1N1) is characterized by rapid transmission among humans and disproportionate infection to children and young adults. Although the pdmH1N1 demonstrated less lethality than initially expected and has now moved into its post-pandemic period, it remains highly possible that through antigenic shift or antigenic drift the pdmH1N1 might re-emerge in the future as a more virulent strain than before, underscoring the need for vaccination prior to an outbreak. Using X-31 ca as a backbone strain, we generated a live attenuated pdmH1N1 vaccine and evaluated its potential as a safe and effective vaccine using mouse and ferret models. Despite an acceptable level of attenuation phenotypes, single dose of immunization with the vaccine efficiently stimulated both systemic and mucosal antibody responses and provided complete protection against lethal challenge with wild type pdmH1N1 virus, even at the lowest immunization dose of 10(3)PFU. The promising results of safety, immunogenicity, and protective efficacy of the vaccine not only contribute to expanding the repertoire of live vaccines as a judicious choice for pandemic H1N1 preparedness, but also suggest the great potential of X-31 ca donor strain to serve as reliable platform for generating diverse live vaccine constructs against seasonal influenza viruses and other pandemic strains.
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