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Infect. Immun. doi:10.1128/IAI.00033-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Bactericidal Antibody Responses Induced by Meningococcal Recombinant Chimeric Factor H Binding Protein Vaccines

Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA

^* To whom correspondence should be addressed. Email: dgranoff{at}chori.org.

	Abstract

Factor H-binding protein (fHbp) is a novel meningococcal vaccine candidate that elicits serum antibodies that activate classical complement pathway bacteriolysis and also inhibit binding of the complement down-regulatory protein, factor H, to the bacterial surface. One limitation of fHbp as a vaccine candidate is antigenic variability since antibodies to fHbp in the variant (v.) 1 antigenic group do not protect against strains expressing v.2 or v.3 proteins, and vice versa. We have identified amino acid residues of epitopes recognized by bactericidal anti-fHbp mAbs prepared against fHbp from each of the v. groups. One epitope expressed by nearly all v.1 proteins mapped to the B domain, while epitopes expressed by fHbp v.2 or v.3 mapped to the C domain. The results provided the rationale for engineering chimeric fHbp molecules containing the A domain, which is conserved across all v. groups, a portion of the B domain of a v.1 protein, and the carboxyl-terminal portion of the B domain and the C domain of a v.2 protein. By ELISA, the resulting recombinant chimeric proteins expressed epitopes from all three variant groups. In mice, the chimeric vaccines elicited serum antibodies with bactericidal activity against a panel of genetically diverse strains expressing fHbp v.1, 2, or 3. The data demonstrate the feasibility of preparing a meningococcal vaccine from a single recombinant protein that elicits broad bactericidal activity, including group B strains that account for 50 percent of cases of meningococcal disease and for which there currently is no broadly protective vaccine.

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• Beernink, P. T., Welsch, J. A., Bar-Lev, M., Koeberling, O., Comanducci, M., Granoff, D. M. (2008). Fine Antigenic Specificity and Cooperative Bactericidal Activity of Monoclonal Antibodies Directed at the Meningococcal Vaccine Candidate Factor H-Binding Protein. Infect. Immun. 76: 4232-4240 [Abstract] [Full Text]