O-Acetylation status of the capsular polysaccharides of serogroup Y and W135 meningococci isolated in the UK.

At a time when tetravalent conjugate vaccines for meningococcal serogroups A/C/Y/W135 are being formulated the O-acetylation status of their respective capsular polysaccharides has not previously been studied in the UK for all components. Although this has been elucidated for serogroup C, little is known about the O-acetylation status of serogroups W135 and Y. Meningococcal serogroup W135 (n=181) and Y (n=90) isolates submitted to the PHLS Meningococcal Reference Unit in 1996, 2000 and 2001 were investigated for O-acetylation capsular status by dot blot assay. Eight per cent of W135 and 79% of Y isolates respectively were found to be O-acetylated with a similar distribution found in both carrier and case isolates. An increase in O-acetylated W135 isolates was noted between 2000 (0%) and 2001 (21%) which was not due to the introduction of the Hajj associated W135 (ET 37 complex; serosubtype P1.5,2) isolates, all of which were de-O-acetylated. Although the biological relevance of O-acetylation status is unknown for these serogroups, an understanding of O-acetylation status of the respective polysaccharides may provide useful insights into the optimal vaccine formulation.

Detection of LP2086 on the cell surface of Neisseria meningitidis and its accessibility in the presence of serogroup B capsular polysaccharide.

The outer membrane protein LP2086, a human factor H binding protein, is undergoing clinical trials as a vaccine against invasive serogroup B meningococcal (MnB) disease. As LP2086 is a surface protein, expression of capsular polysaccharide could potentially limit accessibility of anti-LP2086 antibodies to LP2086 expressed on the surface of bacteria. To determine whether variability in expression levels of the serogroup B capsule (Cap B) might interfere with accessibility of anti-LP2086 antibody binding to LP2086, we evaluated the ability of anti-Cap B and anti-LP2086 antibodies to bind to the surface of 1263 invasive clinical MnB strains by flow cytometry. One of the anti-LP2086 monoclonal antibodies used recognizes virtually all LP2086 sequence variants. Our results show no correlation between the amount of Cap B expressed and the binding of anti-LP2086 antibodies. Furthermore, the susceptibility of MnB bacteria to lysis by anti-LP2086 immune sera was independent of the level of Cap B expressed. The data presented in this paper demonstrates that Cap B does not interfere with the binding of antibodies to LP2086 expressed on the outer membrane of MnB clinical isolates.