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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ASM journals
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 Koeberling, O.
Right arrow Articles by Granoff, D. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Koeberling, O.
Right arrow Articles by Granoff, D. M.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, February 2009, p. 156-162, Vol. 16, No. 2
1071-412X/09/$08.00+0     doi:10.1128/CVI.00403-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Meningococcal Outer Membrane Vesicle Vaccines Derived from Mutant Strains Engineered To Express Factor H Binding Proteins from Antigenic Variant Groups 1 and 2{triangledown}

Oliver Koeberling,1 Serena Giuntini,1 Anja Seubert,1 and Dan M. Granoff2*

Novartis Vaccines, Siena, Italy,1 Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California 946092

Received 6 November 2008/ Returned for modification 8 December 2008/ Accepted 16 December 2008

Meningococcal outer membrane vesicle (OMV) vaccines, which are treated with detergents to decrease endotoxin activity, are safe and effective in humans. However, the vaccines elicit serum bactericidal antibody responses largely directed against PorA, which is antigenically variable. We previously prepared a native (non-detergent-treated) OMV vaccine from a mutant of group B strain H44/76 in which the lpxL1 gene was inactivated, which resulted in penta-acylated lipid A with attenuated endotoxin activity. To enhance protection, we overexpressed factor H binding protein (fHbp) from the antigenic variant 1 group. The vaccine elicited broad serum bactericidal antibody responses in mice against strains with fHbp variant 1 (~70% of group B isolates) but not against strains with variant 2 or 3. In the present study, we constructed a mutant of group B strain NZ98/254 with attenuated endotoxin that expressed both endogenous variant 1 and heterologous fHbp variant 2. A mixture of the two native OMV vaccines from the H44/76 and NZ98/254 mutants stimulated proinflammatory cytokine responses by human peripheral blood mononuclear cells similar to those stimulated by control, detergent-treated OMV vaccines from the wild-type strains. In mice, the mixture of the two native OMV vaccines elicited broad serum bactericidal antibody responses against strains with heterologous PorA and fHbp in the variant 1, 2, or 3 group. By adsorption studies, the principal bactericidal antibody target was determined to be fHbp. Thus, native OMV vaccines from mutants expressing fHbp variants have the potential to be safe for humans and to confer broad protection against meningococcal disease from strains expressing fHbp from each of the antigenic variant groups.

* Corresponding author. Mailing address: Children's Hospital Oakland Research Institute, 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 December 2008.

Clinical and Vaccine Immunology, February 2009, p. 156-162, Vol. 16, No. 2
1071-412X/09/$08.00+0     doi:10.1128/CVI.00403-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Oriente, F., Scarlato, V., Delany, I. (2010). Expression of Factor H Binding Protein of Meningococcus Responds to Oxygen Limitation through a Dedicated FNR-Regulated Promoter. J. Bacteriol. 192: 691-701 [Abstract] [Full Text]  
  • Lucidarme, J., Comanducci, M., Findlow, J., Gray, S. J., Kaczmarski, E. B., Guiver, M., Kugelberg, E., Vallely, P. J., Oster, P., Pizza, M., Bambini, S., Muzzi, A., Tang, C. M., Borrow, R. (2009). Characterization of fHbp, nhba (gna2132), nadA, porA, Sequence Type (ST), and Genomic Presence of IS1301 in Group B Meningococcal ST269 Clonal Complex Isolates from England and Wales. J. Clin. Microbiol. 47: 3577-3585 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»