Carrier-mediated enhancement of cognate T cell help: the basis for enhanced immunogenicity of meningococcal outer membrane protein polysaccharide conjugate vaccine

Haemophilus influenzae type b capsular polysaccharide (PRP) conjugate vacci nes, which are thought to induce T cell-dependent antibody production, indu ce protective responses after a single dose in individuals under 15 months of age. However, multiple doses of these vaccines are required to induce pr otective antibody responses in infants, with the exception of PRP conjugate d to meningococcal outer membrane proteins (OMPC), which does so after a si ngle dose. The basis for this difference is not fully understood, although others have proposed that OMPC and porins, the major protein component of O MPC, act as adjuvants or mitogens. In this report OMPC is shown to enhance CD40 ligand-mediated, T cell-dependent antibody production in mice. This pa ralleled the induction by OMPC of CD86, CD80 and CD40 costimulatory molecul es on human neonatal and murine B cells and of Th1 cytokines. Neither porin s nor lipopolysaccharide fully reproduced the effects of OMPC. These studie s indicate that OMPC acts both as carrier and adjuvant, and thereby enhance s T cell-dependent antibody responses in human infants.