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Infection and Immunity, February 2009, p. 764-769, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01191-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Binding of Complement Factor H (fH) to Neisseria meningitidis Is Specific for Human fH and Inhibits Complement Activation by Rat and Rabbit Sera{triangledown}

Dan M. Granoff,1* Jo Anne Welsch,1 and Sanjay Ram2

Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California 94609,1 Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 016052

Received 25 September 2008/ Returned for modification 14 November 2008/ Accepted 24 November 2008

Complement factor H (fH), a molecule that downregulates complement activation, binds to Neisseria meningitidis and increases resistance to serum bactericidal activity. We investigated the species specificity of fH binding and the effect of human fH on downregulating rat (relevant for animal models) and rabbit (relevant for vaccine evaluation) complement activation. Binding to N. meningitidis was specific for human fH (low for chimpanzee fH and not detected with fH from lower primates). The addition of human fH decreased rat and rabbit C3 deposition on the bacterial surface and decreased group C bactericidal titers measured with rabbit complement 10- to 60-fold in heat-inactivated sera from human vaccinees. Administration of human fH to infant rats challenged with group B strain H44/76 resulted in an fH dose-dependent increase in CFU/ml of bacteria in blood 8 h later (P < 0.02). At the highest fH dose, 50 µg/rat, the geometric mean number of CFU per ml was higher than that in control animals (1,050 versus 43 [P < 0.005]). The data underscore the importance of binding of human fH for survival of N. meningitidis in vitro and in vivo. The species specificity of binding of human fH adds another mechanism toward our understanding of why N. meningitidis is strictly a human pathogen.

* 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 1 December 2008.

Editor: J. N. Weiser

Infection and Immunity, February 2009, p. 764-769, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01191-08
Copyright © 2009, 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]  
  • Plested, J. S., Welsch, J. A., Granoff, D. M. (2009). Ex Vivo Model of Meningococcal Bacteremia Using Human Blood for Measuring Vaccine-Induced Serum Passive Protective Activity. CVI 16: 785-791 [Abstract] [Full Text]  
  • Shaughnessy, J., Lewis, L. A., Jarva, H., Ram, S. (2009). Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein from Neisseria meningitidis and the Binding of Factor H SCR 18 to 20 to Neisseria gonorrhoeae Porin. Infect. Immun. 77: 2094-2103 [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]  


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