Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses

Department of Microbiology, Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2012; 109(7):2573-8. DOI: 10.1073/pnas.1200039109
Source: PubMed


After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk-specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk-specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay.

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    • "The HA mutations could change the epitope to escape the host immune response (Caton et al., 1982; Wiley et al., 1981). Thus, how to elicit the immune response against highly conserved region on HA with broad neutralizing activity is important for vaccine development (Ekiert et al., 2012; Lee et al., 2012; Pica et al., 2012). HA is activated by the proteolytic cleavage of the intact HA (HA0) into HA1 and HA2. "
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    • "542 2014 K. Uranowska and others that they act by preventing the fusion step of viral entry. It was also confirmed that anti-stalk antibodies elicited by infection with the 2009 pH1N1 have contributed to the disappearance of normally circulating H1N1 influenza virus strains in the following season (Pica et al., 2012; Sangster et al., 2013). Antigenically conserved HA stalk domain is thus a promising candidate for preparation of a broadly protective universal influenza vaccine; a potential immunogen that would focus the immune response on the conserved epitopes and would elicit anti-stalk neutralizing antibodies , and may probably give higher protection against different strains of the virus. "
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