title: Genetically modified L3,7 and L2 lipooligosaccharides from Neisseria meningitidis serogroup B confer a broad cross-bactericidal response.
abstract: 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.
authors.affiliation: Research & Development, GlaxoSmithKline Biologicals, Rue de l'Institut 89, B-1330 Rixensart, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Weynants
authors.forename: P
authors.initials: P
authors.lastname: Denoël
authors.forename: N
authors.initials: N
authors.lastname: Devos
authors.forename: D
authors.initials: D
authors.lastname: Janssens
authors.forename: C
authors.initials: C
authors.lastname: Feron
authors.forename: K
authors.initials: K
authors.lastname: Goraj
authors.forename: P
authors.initials: P
authors.lastname: Momin
authors.forename: D
authors.initials: D
authors.lastname: Monnom
authors.forename: C
authors.initials: C
authors.lastname: Tans
authors.forename: A
authors.initials: A
authors.lastname: Vandercammen
authors.forename: F
authors.initials: F
authors.lastname: Wauters
authors.forename: Jan T
authors.initials: JT
authors.lastname: Poolman
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D005260:Female; D055786:Gene Knockout Techniques; D008070:Lipopolysaccharides / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D050296:Microbial Viability; D038541:Neisseria meningitidis, Serogroup B / Q000737:chemistry* / Q000276:immunology*; D018272:Porins / Q000235:genetics; D022142:Secretory Vesicles / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D008070:Lipopolysaccharides; D018272:Porins; C023023:lipid-linked oligosaccharides; C057699:porin protein, Neisseria