1. An influenza H1 hemagglutinin stem-only immunogen elicits a broadly cross-reactive B cell response in humans.
- Author
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Andrews, Sarah F., Cominsky, Lauren Y., Shimberg, Geoffrey D., Gillespie, Rebecca A., Gorman, Jason, Raab, Julie E., Brand, Joshua, Creanga, Adrian, Gajjala, Suprabhath R., Narpala, Sandeep, Cheung, Crystal S. F., Harris, Darcy R., Zhou, Tongqing, Gordon, Ingelise, Holman, LaSonji, Mendoza, Floreliz, Houser, Katherine V., Chen, Grace L., Mascola, John R., and Graham, Barney S.
- Subjects
IMMUNOGLOBULINS ,B cells ,IMMUNOLOGIC memory ,VACCINE trials ,HEMAGGLUTININ ,INFLUENZA ,SEASONAL influenza - Abstract
Current yearly seasonal influenza vaccines primarily induce an antibody response directed against the immunodominant but continually diversifying hemagglutinin (HA) head region. These antibody responses provide protection against the vaccinating strain but little cross-protection against other influenza strains or subtypes. To focus the immune response on subdominant but more conserved epitopes on the HA stem that might protect against a broad range of influenza strains, we developed a stabilized H1 stem immunogen lacking the immunodominant head displayed on a ferritin nanoparticle (H1ssF). Here, we evaluated the B cell response to H1ssF in healthy adults ages 18 to 70 in a phase 1 clinical trial (NCT03814720). We observed both a strong plasmablast response and sustained elicitation of cross-reactive HA stem–specific memory B cells after vaccination with H1ssF in individuals of all ages. The B cell response was focused on two conserved epitopes on the H1 stem, with a highly restricted immunoglobulin repertoire unique to each epitope. On average, two-thirds of the B cell and serological antibody response recognized a central epitope on the H1 stem and exhibited broad neutralization across group 1 influenza virus subtypes. The remaining third recognized an epitope near the viral membrane anchor and was largely limited to H1 strains. Together, we demonstrate that an H1 HA immunogen lacking the immunodominant HA head produces a robust and broadly neutralizing HA stem–directed B cell response. Fighting flu: A major goal for influenza vaccines is to elicit broadly reactive immune responses that can protect against many strains of the virus. Widge et al. and Andrews et al. report results of a phase 1 clinical trial testing a vaccine that may get closer to this goal. Widge et al. demonstrated that immunization with one or two doses of an H1 hemagglutinin stabilized stem nanoparticle (H1ssF) vaccine was safe in recipients and elicited durable neutralizing antibody responses. Andrews et al. found that memory B cell responses elicited by H1ssF vaccination were broadly cross-reactive and targeted two conserved epitopes on the H1 stem. Together, these studies highlight the potential of H1ssF and similar stem-only immunogens as influenza vaccines. —CM [ABSTRACT FROM AUTHOR]
- Published
- 2023
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