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An influenza H1 hemagglutinin stem-only immunogen elicits a broadly cross-reactive B cell response in humans. | LitMetric

AI Article Synopsis

  • Current seasonal flu vaccines trigger strong antibody responses mainly against the highly variable head region of the hemagglutinin (HA) protein, providing limited protection against other strains.
  • Researchers created a new immunogen (H1ssF) that targets the more stable stem region of HA, potentially offering broader protection against various influenza strains.
  • In a phase 1 clinical trial, participants showed strong B cell responses focused on conserved epitopes in the HA stem, indicating the potential of H1ssF to generate widely neutralizing immunity against different influenza subtypes.

Article 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.

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Source
http://dx.doi.org/10.1126/scitranslmed.ade4976DOI Listing

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