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Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp

Author

Listed:
  • Jacinto López-Sagaseta

    (GSK Vaccines srl)

  • Peter T. Beernink

    (UCSF Benioff Children’s Hospital)

  • Federica Bianchi

    (GSK Vaccines srl)

  • Laura Santini

    (GSK Vaccines srl)

  • Elisabetta Frigimelica

    (GSK Vaccines srl)

  • Alexander H. Lucas

    (UCSF Benioff Children’s Hospital)

  • Mariagrazia Pizza

    (GSK Vaccines srl)

  • Matthew J. Bottomley

    (GSK Vaccines)

Abstract

Data obtained recently in the United Kingdom following a nationwide infant immunization program against serogroup B Neisseria meningitidis (MenB) reported >80% 4CMenB vaccine-mediated protection. Factor H-binding protein (fHbp) is a meningococcal virulence factor and a component of two new MenB vaccines. Here, we investigated the structural bases underlying the fHbp-dependent protective antibody response in humans, which might inform future antigen design efforts. We present the co-crystal structure of a human antibody Fab targeting fHbp. The vaccine-elicited Fab 1A12 is cross-reactive and targets an epitope highly conserved across the repertoire of three naturally occurring fHbp variants. The free Fab structure highlights conformational rearrangements occurring upon antigen binding. Importantly, 1A12 is bactericidal against MenB strains expressing fHbp from all three variants. Our results reveal important immunological features potentially contributing to the broad protection conferred by fHbp vaccination. Our studies fuel the rationale of presenting conserved protein epitopes when developing broadly protective vaccines.

Suggested Citation

  • Jacinto López-Sagaseta & Peter T. Beernink & Federica Bianchi & Laura Santini & Elisabetta Frigimelica & Alexander H. Lucas & Mariagrazia Pizza & Matthew J. Bottomley, 2018. "Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02827-7
    DOI: 10.1038/s41467-018-02827-7
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