Immunization with meningococcal outer-membrane protein vesicles containing lipooligosaccharide protects mice against lethal experimental group B Neisseria meningitidis infection and septic shock.
Detergent-treated group B Neisseria meningitidis outer membrane vesicles (D-OMVs) from wild-type M986 and from nonencapsulated mutant M986-non-capsule variant (NCV) were compared as immunogens. Eight weeks after 3 consecutive immunizations with the immunogens, mice were challenged with a lethal dose of purified endotoxin or heat-killed or living N. meningitidis, plus d-galactosamine (400 mg/kg). D-OMVs from M986 induced bactericidal antibodies to both M986 (B : 2a : P1.5,2 : L3,7) and 6275 (B : 2a : P1.2,5 : L3) and protected the animals against both strains, whereas D-OMVs from M986-NCV did not protect the animals against infection with 6275 even when high serum bactericidal activity was induced. Tumor necrosis factor-alpha detected after bacterial infection was high in both protected and unprotected mice; interleukin (IL)-6 was high in mice that died but low in animals that survived. Exogenous administration of recombinant mouse IL-6 reversed the immunogens' protective effects. Protection against infection in mice does not necessarily correlate with the measured levels of serum bactericidal antibody alone, opsonic antibody alone, or cytokine profile alone. A comprehensive assessment of the preclinical efficacy of group B outer-membrane protein vaccines should include monitoring humoral antibodies, cytokine response, and protective effects against lethal infection.
Quakyi
E K
EK
Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. earth9@straubing.baynet.de
Frasch
C E
CE
Buller
N
N
Tsai
C M
CM
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D008070:Lipopolysaccharides / Q000276:immunology*; D008589:Meningococcal Infections / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology*; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis; D012703:Serotyping; D012772:Shock, Septic / Q000276:immunology / Q000517:prevention & control*; D013045:Species Specificity; D015996:Survival Rate
D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides