| Popis: |
Neisseria meningitidis (NM) is a major pathogen associated with severe and often fatal meningitis and septicaemia world-wide. Effective vaccines based on the capsular antigens for serogroups A,C,W135 and Y are available. The capsule of serogroup B, responsible for much of the endemic disease in industrialised countries, is not immunogenic and other approaches to development of an effective vaccine are being examined. Carriage of the commensal species Neisseria lactamica (NL) and Moraxella catarrhalis (MC) coincides with progressive increase in the level of natural immunity against NM. The aims of this project were: 1) to identify strains of NL and MC expressing antigens cross-reactive with NM; 2) to assess the functions of the cross-reactive antibodies induced by the commensal, e.g., complement mediated lysis and phagocytosis or neutralisation of lipooligosaccharide (LOS) toxicity; 3) to identify the antigens inducing cross-reactive antibodies; 4) to develop a model system using human cells to assess toxicity of vaccine candidates and their ability to induce neutralising or opsonic antibodies. Commensal isolates from different regions of Europe were used to absorb pooled human serum from individuals with no history of meningococcal disease. The pool had antibodies bactericidal against meningococcal isolates expressing a variety of phenotypes. These included isolates from patients, carriers and reference strains expressing different lipooligosaccharide (LOS) determinants. Strain NL1 from Scotland absorbed bactericidal antibodies against the greatest number of NM isolates and a broad range of phenotypes. Strain NL6 from Greece absorbed antibodies against only a few NM strains and isolates from Iceland and the Czech Republic showed intermediate patterns of absorption. Strain MC1 absorbed bactericidal and opsonising activities against significantly more NM strains expressing different phenotypes than strain MC2. |
