This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Weynants, V. E.
Right arrow Articles by Poolman, J. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Weynants, V. E.
Right arrow Articles by Poolman, J. T.

 Previous Article  |  Next Article 

Infection and Immunity, November 2007, p. 5434-5442, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00411-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Additive and Synergistic Bactericidal Activity of Antibodies Directed against Minor Outer Membrane Proteins of Neisseria meningitidis{triangledown}

Vincent E. Weynants,1 Christiane M. Feron,1 Karine K. Goraj,1 Martine P. Bos,2 Philippe A. Denoël,1 Vincent G. Verlant,1 Jan Tommassen,2 Ian R. A. Peak,3 Ralph C. Judd,4 Michael P. Jennings,5 and Jan T. Poolman1*

GlaxoSmithKline Biologicals, B-1330 Rixensart, Belgium,1 Department of Molecular Microbiology, Utrecht University, 3584-CH Utrecht, The Netherlands,2 Institute for Glycomics, Griffith University, Southport QLD 4215, Australia,3 Division of Biological Sciences, University of Montana, Missoula, Montana 59812,4 School of Molecular & Microbial Sciences, University of Queensland, Brisbane QLD 4072, Australia5

Received 20 March 2007/ Returned for modification 1 May 2007/ Accepted 16 July 2007

Neisseria meningitidis serogroup B is a major cause of bacterial meningitis in younger populations. The available vaccines are based on outer membrane vesicles obtained from wild-type strains. In children less than 2 years old they confer protection only against strains expressing homologous PorA, a major, variable outer membrane protein (OMP). We genetically modified a strain in order to eliminate PorA and to overproduce one or several minor and conserved OMPs. Using a mouse model mimicking children's PorA-specific bactericidal activity, it was demonstrated that overproduction of more than one minor OMP is required to elicit antibodies able to induce complement-mediated killing of strains expressing heterologous PorA. It is concluded that a critical density of bactericidal antibodies needs to be reached at the surface of meningococci to induce complement-mediated killing. With minor OMPs, this threshold is reached when more than one antigen is targeted, and this allows cross-protection.

* Corresponding author. Mailing address: Research & Development, GlaxoSmithKline Biologicals, Rue de l'Institut 89, B-1330 Rixensart, Belgium. Phone: 32-(0)2-656 9847. Fax: 32-(0)2-656 8113. E-mail: jan.poolman{at}gskbio.com

{triangledown} Published ahead of print on 30 July 2007.

Editor: J. N. Weiser

Infection and Immunity, November 2007, p. 5434-5442, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00411-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Weynants, V., Denoel, P., Devos, N., Janssens, D., Feron, C., Goraj, K., Momin, P., Monnom, D., Tans, C., Vandercammen, A., Wauters, F., Poolman, J. T. (2009). Genetically Modified L3,7 and L2 Lipooligosaccharides from Neisseria meningitidis Serogroup B Confer a Broad Cross-Bactericidal Response. Infect. Immun. 77: 2084-2093 [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]  
  • 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]  
  • Beernink, P. T., Granoff, D. M. (2008). Bactericidal Antibody Responses Induced by Meningococcal Recombinant Chimeric Factor H-Binding Protein Vaccines. Infect. Immun. 76: 2568-2575 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»