A novel method for enhancement of T independent responses.

Bacterial capsular polysaccharides are the major targets for vaccination against encapsulated bacteria but present problems when used for immunisation as they are T cell independent antigens (TI-II). TI-II antigens do not induce a memory response, but induce an antibody response which is of low magnitude and is predominantly IgM, with little or no isotype switching to IgG isotypes. This is because TI-II antigens do not induce T cell help. Such T cell help to B cells is mediated through up regulation of the CD40 ligand (CD154) on the activated T cell, which binds to CD40 inducing B cell activation, proliferation and isotype switching in conjunction with cytokines produced by the T cell. We have successfully mimicked this T cell help and induced very strong, isotype switched antibody responses to TI-II antigens by the simple addition of agonistic anti-CD40 antibodies to pneumococcal polysaccharides before immunisation.