Secreted proteins of Neisseria meningitidis protect mice against infection.
We addressed the hypothesis that meningococcal secreted proteins (MSPs) can elicit protective immunity against meningococcal disease. Endotoxin-depleted MSP preparations were used to immunise a group of 15 six-week-old BALB/c mice (25microg MSPs/dose mixed with Freund's complete adjuvant) on days 0, 14 and 21. Mice were challenged 2 weeks later with 10(7) colony forming units of live Neisseria meningitidis strain MC58 (serogroup B, ET-5). Negative and positive control groups of 15 mice each were injected with adjuvant only, or a live attenuated strain of MC58, respectively. Seven out of 15 mice (47%) from the negative control group died after 72h of challenge, whereas none of test or positive control group died. Protection afforded by the anti-MSP immune response can be at least partly attributed to complement-mediated bacterial lysis, detectable in vitro using the serum of immunised mice. Murine anti-MC58 MSP sera were bactericidal against homologous and five unrelated ET-5 serogroup B strains. However, failed to kill strains from other hypervirulent clonal lineages belonging to the same or different serogroups, despite the presence of cross-reactive antibodies detectable by immunoblotting. Similar sera raised against MSPs from an isolate belonging to the ET-37 electropherotype lineage were bactericidal against all tested isolates of this lineage and, in addition, against some but not all isolates belonging to the ET-5 lineage. FACS analysis of intact bacteria treated with anti-MSPs confirmed surface-binding of antibodies.
Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
Yanwen
Y
Li
Karl G
KG
Wooldridge
Muhammad A
MA
Javed
Christoph M
CM
Tang
Dlawer A A
DA
Ala'aldeen
D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D001433:Bacteriolysis / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000378:metabolism; D007115:Immunization Schedule; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology / Q000378:metabolism; D015610:Serum Bactericidal Test
D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D007106:Immune Sera; D022401:Meningococcal Vaccines