Epitope mapping of a cross-reactive monoclonal antibody against the factor H-binding protein of Neisseria meningitidis

A. Castello, I. Costa, I. Pernice, R. Galbo, O. Romeo, D. Granoff, Carla Lo Passo

Research output: Contribution to journalArticlepeer-review

Abstract

Neisseria meningitidis is an encapsulated gram-negative bacterium, major cause of bacterial meningitis and sepsi worldwide. Although polysaccharide- protein conjugated vaccines are available for the prevention of diseases caused by strains with group A, C, W-135 or Y capsules, no broadly protective vaccine is available against group B strains. The factor H binding protein (fHbp), a 27-kDa membrane-anchored lipoprotein of Neisseria meningitidis, is a promising vaccine candidate that elicits serum bactericidal antibodies in humans. The presence of factor H (fH) on the bacterial surface is critical to circumvent host defense while, in the absence of bound fH, the organism becomes susceptible to bacteriolysis. Based on sequence variability of the entire protein, fHbp has been divided into three variant groups or two sub-families. A panel of antifHbp mAbs has been produced from mice immunized with the 3 variants of fHbp and their epitopes were previously mapped, except for the mAb designated JAR36, a murine IgG mAb isolated from a mouse immunized with variant 3. In this study, we report epitope mapping of JAR36, this mAb cross-reacts with all fHbp sequences in V.2 and V.3 groups, binds to the bacterial surface and elicits complement-mediated bactericidal activity in combination with other anti-fHbp mAbs. We screened bacteriophage- displayed random peptide libraries to identify amino acid residues contributing to the JAR36 epitope. Mapping predictions were validated by constructing, through site-specific mutagenesis, corresponding rfHbps single-point variants, and analyzing their reactivity with the mAb.

Original languageEnglish
Pages (from-to)43-44
Number of pages2
JournalJournal of Biological Research (Italy)
Volume88
Issue number1
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry, medical
  • Plant Science

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