A Broadly Cross-Reactive Monoclonal Antibody Against an Epitope on the N-terminus of Meningococcal fHbp
Open Access
- 28 March 2012
- journal article
- research article
- Published by Springer Nature in Scientific Reports
- Vol. 2 (1) , 341
- https://doi.org/10.1038/srep00341
Abstract
Meningococcal factor H binding protein (fHbp) is an important vaccine antigen for prevention of disease caused by capsular group B strains. The protein has been sub-classified into three variant groups. Most anti-fHbp antibodies are variant group-specific and recognize epitopes on the C-terminal domain. We report a murine IgG1 mAb, JAR 41, which broadly cross-reacted with fHbp sequence variants from all variant groups. The mAb bound to the surface of live meningococci with fHbp from each of the three variant groups. In combination with second non-bactericidal anti-fHbp mAbs, JAR 41 elicited complement-mediated bactericidal activity in vitro, and augmented passive protection against meningococcal bacteremia in human fH transgenic rats. The epitope was located on a conserved region of the N-terminal portion of the fHbp molecule opposite that of fH contact residues. The data underscore the importance of broadly cross-reactive, surface-exposed epitopes on the N-terminal domain in the design of protective fHbp vaccines.Keywords
This publication has 44 references indexed in Scilit:
- Cooperative serum bactericidal activity between human antibodies to meningococcal factor H binding protein and Neisserial heparin binding antigenVaccine, 2011
- Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccinesProceedings of the National Academy of Sciences, 2010
- Review of Meningococcal Group B VaccinesClinical Infectious Diseases, 2010
- Frequency of factor H-binding protein modular groups and susceptibility to cross-reactive bactericidal activity in invasive meningococcal isolatesVaccine, 2009
- A region of the N-terminal domain of meningococcal factor H-binding protein that elicits bactericidal antibody across antigenic variant groupsMolecular Immunology, 2009
- Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal diseaseVaccine, 2009
- Solution Structure of the Factor H-binding Protein, a Survival Factor and Protective Antigen of Neisseria meningitidisJournal of Biological Chemistry, 2009
- Structural Basis for the Immunogenic Properties of the Meningococcal Vaccine Candidate LP2086Journal of Biological Chemistry, 2009
- Neisseria meningitidis recruits factor H using protein mimicry of host carbohydratesNature, 2009
- A universal vaccine for serogroup B meningococcusProceedings of the National Academy of Sciences, 2006