Activity and cross-reactivity of antibodies induced in mice by immunization with a group B meningococcal conjugate

The capsular polysaccharide of group B Neisseria meningitidis is composed o f a linear homopolymer of alpha (2-8) N-acetyl neuraminic acid or polysiali c acid (PSA) that is also carried by isoforms of the mammalian neural cell adhesion molecule (NCAM), which is especially expressed on brain cells duri ng development. Here we analyzed the ability of antibodies induced by the c andidate vaccine N-propionyl polysaccharide tetanus toxoid conjugate to rec ognize PSA-NCAM. We hyperimmunized mice to produce a pool of antisera and a series of immunoglobulin G monoclonal antibodies and evaluated their self- reactivity profile by using a battery of tests (immunoprecipitation, immuno blotting, and immunofluorescence detection on live cells and human tissue s ections) chosen for their sensitivity and specificity to detect PSA-NCAM in various environments. We also searched for the effects of the vaccine-indu ced antibodies in two functional assays involving cell lysis or cell migrat ion. Although they were highly bactericidal, all the antibodies tested show ed very low or no recognition of PSA-NCAM, in contrast to PSA-specific mono clonal antibodies used as controls. Different patterns of cross-reactions w ere revealed by the tests used, likely due to affinity and specificity diff erences among the populations of induced antibodies. Furthermore, neither c ell lysis nor perturbation of migration was observed in the presence of the tested antibodies. Importantly, we showed that whereas enzymatic removal o f PSA groups from the surfaces of live cells perturbed their migration, blo cking them with PSA-specific antibodies was not functionally detrimental. T aken together, our data indicated that this candidate vaccine induced antib odies that could not demonstrate an immunopathologic effect.