Additive and synergistic bactericidal activity of antibodies directed against minor outer membrane proteins of Neisseria meningitidis.
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.
GlaxoSmithKline Biologicals, Rue de l'Institut 89, B-1330 Rixensart, Belgium.
Vincent E
VE
Weynants
Christiane M
CM
Feron
Karine K
KK
Goraj
Martine P
MP
Bos
Philippe A
PA
Denoël
Vincent G
VG
Verlant
Jan
J
Tommassen
Ian R A
IR
Peak
Ralph C
RC
Judd
Michael P
MP
Jennings
Jan T
JT
Poolman
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000907:Antibodies, Bacterial / Q000494:pharmacology*; D001770:Blood Bactericidal Activity; D004357:Drug Synergism; D005260:Female; D017353:Gene Deletion; D008565:Membrane Proteins / Q000276:immunology*; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D050296:Microbial Viability; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology*; D018272:Porins / Q000235:genetics
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D008565:Membrane Proteins; D018272:Porins; C057699:porin protein, Neisseria