2015
DOI: 10.1038/nm.3927
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Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection

Abstract: The antibody response to influenza is primarily focused on the head region of the hemagglutinin (HA) glycoprotein, which in turn undergoes antigenic drift, thus necessitating annual updates of influenza vaccines. In contrast, the immunogenically subdominant stem region of HA is highly conserved and recognized by antibodies capable of binding multiple HA subtypes. Here we report the structure-based development of an H1 HA stem-only immunogen that confers heterosubtypic protection in mice and ferrets. Six iterat… Show more

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Cited by 610 publications
(761 citation statements)
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“…While both humoral and cellular immunity can mediate heterosubtypic responses, inducing antibodies against the more conserved stalk domain of hemagglutinin (HA) has been the recent focus of many vaccine programmes (10,11). However, multipronged approaches, targeting several antigens inducing both humoral and cellular responses may limit the generation of viral escape mutants compared to vaccines targeting a limited number of protective epitopes on the HA stalk .…”
Section: Introductionmentioning
confidence: 99%
“…While both humoral and cellular immunity can mediate heterosubtypic responses, inducing antibodies against the more conserved stalk domain of hemagglutinin (HA) has been the recent focus of many vaccine programmes (10,11). However, multipronged approaches, targeting several antigens inducing both humoral and cellular responses may limit the generation of viral escape mutants compared to vaccines targeting a limited number of protective epitopes on the HA stalk .…”
Section: Introductionmentioning
confidence: 99%
“…A number of studies have now firmly established that stalk-specific bnAbs, normally present in low quantities, can be boosted substantially in humans following exposure to HA subtypes with antigenically foreign head domains (2)(3)(4)(5)(6)(7)(8). Sequential vaccination of animals with chimeric HAs or with "headless" vaccine constructs have effectively recapitulated the boosting of bnAbs observed in humans after exposure to foreign HAs, and also are protective against heterologous and heterosubtypic IAV challenge (9)(10)(11)(12)(13)(14)(15). These strategies are now being tested as promising "universal" influenza virus vaccine candidates (16).…”
mentioning
confidence: 99%
“…The ability to establish high titers of broadly neutralizing antibodies directed against the HA stalk is a critical component in developing a broad-spectrum universal influenza virus vaccine (14)(15)(16)(17)(18). However, the in vitro neutralizing activity of stalk-specific monoclonal antibodies (mAbs) is generally inferior to that of hemagglutination-inhibiting mAbs, and differences in their inhibitory concentrations can approach 2-to 3-log differences (19,20).…”
mentioning
confidence: 99%