Open AccessGenetically Modified L3,7 and L2 Lipooligosaccharides from Neisseria meningitidis Serogroup B Confer a Broad Cross-Bactericidal Response
Author(s) -
Vincent Weynants,
Philippe Denoël,
Nathalie Devos,
Dominique Janssens,
Christiane Feron,
Karine Goraj,
P. Momin,
D. Monnom,
Christine Tans,
Annick Vandercammen,
Florence Wauters,
Jan Poolman
Publication year - 2009
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01108-08
Subject(s) - neisseria meningitidis , reactogenicity , bacterial outer membrane , microbiology and biotechnology , biology , antigen , neisseriaceae , meningococcal vaccine , antibody , virology , meningococcal disease , neisseria , gene , immunogenicity , bacteria , escherichia coli , antibiotics , genetics
Currently availableNeisseria 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 modifiedporA 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 algtB mutation; truncated L3 LOS), but not LOS produced without thegalE 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.