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Infection and Immunity, May 2009, p. 2084-2093, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01108-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Genetically Modified L3,7 and L2 Lipooligosaccharides from Neisseria meningitidis Serogroup B Confer a Broad Cross-Bactericidal Response{triangledown}

V. Weynants, P. Denoël, N. Devos, D. Janssens, C. Feron, K. Goraj, P. Momin, D. Monnom, C. Tans, A. Vandercammen, F. Wauters, and Jan T. Poolman*

GlaxoSmithKline Biologicals, Rixensart B 1330, Belgium

Received 5 September 2008/ Returned for modification 3 November 2008/ Accepted 5 March 2009

Currently available Neisseria meningitidis serogroup B (MenB) vaccines are based on outer membrane vesicles (OMVs) that are obtained from wild-type strains. They are purified with the aim of decreasing the lipooligosaccharide (LOS) content and hence reduce the reactogenicity of the vaccine even though LOS is a potential protective antigen. In <2-year-old children, these MenB vaccines confer protection only against strains expressing homologous PorA, a major and variable outer membrane protein. Our objective was to develop a safe LOS-based vaccine against MenB. To this end, we used modified porA knockout strains expressing genetically detoxified (msbB gene-deleted) L2 and L3,7 LOSs, allowing the production of LOS-enriched OMVs. The vaccine-induced antibodies were found to be bactericidal against nearly all invasive strains, irrespective of capsular serogroup. In addition, we have also demonstrated that LOS lacking the terminal galactose (with a lgtB mutation; truncated L3 LOS), but not LOS produced without the galE gene, induced a bactericidal antibody response in mice similar to that seen for LOS containing the full lacto-N-neotetraose (L3,7 LOS). In conclusion, a bivalent detoxified LOS OMV-based vaccine demonstrated the potential to afford a broad cross-protection against meningococcal disease.

* 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 8436. E-mail: jan.poolman{at}gskbio.com

{triangledown} Published ahead of print on 16 March 2009.

Editor: R. P. Morrison

Infection and Immunity, May 2009, p. 2084-2093, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01108-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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