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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    ABSTRACT: Shigellosis, caused by Shigella is the most common cause of bacillary dysentery. The disease is associated with high morbidity and mortality rate owing to its multiple drug resistance. Hence recovery from the disease would primarily depend on the development of an effective immune-modulator for strong mucosal immune response. The role of cellular immunity may be a critical factor in protection against shigellosis as Shigella remains an intracellular pathogen during most of its life-cycle. Development of a potent immunomodulator may provide strong and longlasting immunity to shigellosis. In this review, we have attempted to highlight the disease dimension and its deviation due to the effect of various Shigella surface antigens that would help in the development of an effective immune response. Cellular innate immune modulation will be a new generation target for the development of mucosal candidate vaccines where proper receptor activation such as Toll-Like Receptors (TLRs), Cytokine Receptors (CyRs) and/or T-Cell Receptors (TCRs) on the host cell could be aimed at producing mucosal immunity. An effort has been made to better understand the effect of these immunomodulators against shigellosis by way of modulating the host immune mechanism to Shigella outer membrane component. © 2015 Ashim K. Bagchi, Rushita A. Bagchi, Dipak K. Hens, Fahmida Jahan, Pragna H. Parikh and Dhira Rani Saha.
    Full-text · Article · Jun 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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    ABSTRACT: There is a critical need for new influenza vaccines able to protect against constantly emerging divergent virus strains. This will be sustained by the induction of vigorous cellular responses and humoral immunity capable of acting at the portal of entry of this pathogen. In this study we evaluate the protective efficacy of intranasal vaccination with recombinant influenza nucleoprotein (rNP) co-administrated with bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) as adjuvant. Immunization of BALB/c mice with two doses of the formulation stimulates high titers of NP-specific IgG in serum and secretory IgA at mucosal sites. This formulation also promotes a strong Th1 response characterized by high secretion of INF-γ and IL-2. The immune response elicited promotes efficient protection against virus challenge. These results suggest that c-di-AMP is a potent mucosal adjuvant which may significantly contribute towards the development of innovative mucosal vaccines against influenza.
    Full-text · Article · Aug 2014 · PLoS ONE
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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.
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