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Infection and Immunity, June 2008, p. 2568-2575, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00033-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Bactericidal Antibody Responses Induced by Meningococcal Recombinant Chimeric Factor H-Binding Protein Vaccines{triangledown}

Peter T. Beernink and Dan M. Granoff*

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

Received 9 January 2008/ Returned for modification 15 February 2008/ Accepted 20 February 2008

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 1 (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 monoclonal antibodies prepared against fHbp from each of the variant 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 variant 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 enzyme-linked immunosorbent assay, 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, v.2, or v.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, which account for 50 percent of cases of meningococcal disease and for which there currently is no broadly protective vaccine.

* Corresponding author. Mailing address: 5700 Martin Luther King Jr. Way, Oakland, CA 94609. Phone: (510) 450-7640. Fax: (510) 450-7915. E-mail: dgranoff{at}chori.org

{triangledown} Published ahead of print on 24 March 2008.

Editor: J. N. Weiser

Infection and Immunity, June 2008, p. 2568-2575, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00033-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Beernink, P. T., Granoff, D. M. (2009). The modular architecture of meningococcal factor H-binding protein. Microbiology 155: 2873-2883 [Abstract] [Full Text]  
  • Koeberling, O., Giuntini, S., Seubert, A., Granoff, D. M. (2009). Meningococcal Outer Membrane Vesicle Vaccines Derived from Mutant Strains Engineered To Express Factor H Binding Proteins from Antigenic Variant Groups 1 and 2. CVI 16: 156-162 [Abstract] [Full Text]  
  • Seib, K. L., Serruto, D., Oriente, F., Delany, I., Adu-Bobie, J., Veggi, D., Arico, B., Rappuoli, R., Pizza, M. (2009). Factor H-Binding Protein Is Important for Meningococcal Survival in Human Whole Blood and Serum and in the Presence of the Antimicrobial Peptide LL-37. Infect. Immun. 77: 292-299 [Abstract] [Full Text]  
  • 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]  


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