5O14

Co-crystal structure of a cross-reactive bactericidal human antibody targeting meningococcal vaccine antigen factor H binding protein

Summary for 5O14

• Entry DOI: 10.2210/pdb5o14/pdb
• Descriptor: Factor H binding protein variant 1.1, Fab 1A12 Heavy Chain, Fab 1A12 Light Chain, ... (6 entities in total)
• Functional Keywords: human fab, factor h binding protein, outer membrane, infection, immune system
• Biological source: Neisseria meningitidis serogroup B (strain MC58); More
• Total number of polymer chains: 6
• Total formula weight: 153920.80

Authors

Lopez-Sagaseta, J. (deposition date: 2017-05-18, release date: 2018-02-14, Last modification date: 2024-11-13)

Primary citation

Lopez-Sagaseta, J.,Beernink, P.T.,Bianchi, F.,Santini, L.,Frigimelica, E.,Lucas, A.H.,Pizza, M.,Bottomley, M.J.
Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp.
Nat Commun, 9:528-528, 2018

PubMed 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.

PubMed: 29410413
DOI: 10.1038/s41467-018-02827-7

Experimental method

X-RAY DIFFRACTION (2.195 Å)