The capsular PS of Neisseria meningitidis group C (MCPS) is a homopolymer of a(2--9) linked sialic acid. The PS is a TI antigen which is poorly immunogenic in infants and young children. We showed earlier that the immune response to MCPS of BALB/c mice provides a model system which closely parallels the response to MCPS in man. Here we compare the BALB/c response to MCPS with that to an MCPS-tetanus toxoid (MCPS- TT) conjugate, a TD form of the antigen. Differences in the isotype of the serum antibody response to MCPS or MCPS-TT have been extended to examine the response of purified B and T lymphocytes taken from animals unprimed or primed with MCPS or MCPS-TT, transferred to irradiated recipients and boosted with MCPS, MCPS-TT or a mixture of MCPS and TT. To date, the results indicate that MCPS-TT primed B cells have switched to produce IgG1 antibody and are memory cells that can be boosted to produce IgG1 antibody by either MCPS, the covalent MCPS-TT or the mixture of MCPS plus TT. Because we had previously observed that the large increase in serum IgG1 antibody to MCPS seen after immunization with MCPS-TT but not MCPS, itself, was not accompanied by a similar increase in the idiotypes found on naturally occurring anti-MCPS, we have generated a panel of monoclonal anti-MCPS antibodies from mice immunized with MCPS-TT. Six of the eight are IgG1(k), one is IgG2b(k) and the other is an IgA(k). These antibodies will be purified and examined in detail for fine specificity using polysaccharides structurally related to MCPS. They will be further tested for bactericidal capacity because MCPS-TT immunization results in a large increase in serum bactericidal activity and we want to determine if these IgG1 mAb are able to kill bacteria in a complement-dependent fashion. Finally, the mAb will be used to raise anti-idiotypic antibodies which may provide serotypic markers of thymus-dependent antibodies specific for MCPS. These reagents will be invaluable in examining whether thymus independent and thymus-dependent forms of polysaccharides stimulate the same antibody forming cells.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BA002005-05
Application #
3810960
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost