Structural Biology

Biography

Biography: Jacinto López-Sagaseta

Abstract

Anchored yet exposed to the outside moiety of the bacterial shell, Factor H   binding protein   (fHbp) is one of the main  antigenic  components of Neisseria meningitidis, one of the causative agents of   men ingitis  , an infect ious disease that can cause a fatal outcome or permanent disability within 24 hours of infection. Though there have been described up to three different variants of fHbp, it is fHbp variant 1 (fHbp-1), the subclass showing the highest prevalence amongst MenB strains, and also, one of the actual components of Bexsero, the current licensed vaccine against   serogroup   B Meningococci (MenB). In order to define the structural basis that underlie the recognition of this  highly immunogenic antigen and the broad strain coverage offered by Bexsero, we have determined the crystal structure of a complex between a human Fab and fHbp-1 at a resolution of 2.2 Å. The Fab has been originated from an immunization study that included a recombinant form of fHbp-1, and importantly, it is cross-reactive against all of them. The cross-reactive  epitope  spans along the c-terminal beta barrel of fHbp and encompasses residues that are highly conserved across the different fHbp variants. The hypervariable CDR3 loop of the heavy chain dominates the recognition of the antigen. This crystal structure represents the first evidence, at the atomic level, of the recognition of Neisseria meningitidis fHbp by a human Fab r  aised in an individual upon vaccination, and provides the basis behind the broad strain coverage of the current vaccine against MenB. In addition, the information gathered from this structure will be of high value for future structure-based antigen design.