Meningococcal polysaccharide-protein conjugate vaccines

Abstract

Meningococcal oligosaccharide- and polysaccharide-protein conjugate vaccines are under investigation in humans for prevention of disease caused by serogroup A and C organisms. These vaccines appear to be safe and well tolerated. Repeated immunization of infants and toddlers with meningococcal C conjugate vaccines, given either alone or in a single formulation with meningococcal A conjugate vaccine, elicits boostable increases in serum meningococcal C bactericidal antibody titer. The C conjugate vaccine also induces memory B cells that are capable of responding to a subsequent immunization with unconjugated meningococcal polysaccharide vaccine. In contrast, immunization with unconjugated meningococcal C polysaccharide vaccine in these age groups is much less immunogenic and does not induce long-term immunologic memory. Less data are available on immune responses to meningococcal A conjugate vaccines. However, toddlers vaccinated in the United States with a meningococcal A vaccine combined with a meningococcal C conjugate vaccine, show much higher meningococcal A bactericidal antibody responses and greater induction of memory B cells than control toddlers given unconjugated meningococcal polysaccharide vaccine. The same conjugate vaccine was given to infants in Gambia, where there were no significant differences in the magnitude of the anti-A antibody responses, or in induction of memory B cells, compared to control infants given unconjugated polysaccharide vaccine. Meningococcal B conjugate vaccines also are under development. In experimental animals, these vaccines are much less immunogenic than A or C conjugates, probably because of immunologic tolerance induced to the B polysaccharide by exposure to cross-reacting polysialic acid expressed in the brain and other tissues of the host. To circumvent tolerance, conjugate vaccines have been prepared from derivatized meningococcal B polysaccharide, where N-propionyl groups have been substituted for N-acetyl groups. In experimental animals, such conjugates show increased immunogenicity, including development of bactericidal antibodies, but a subset of the antibodies still shows strong autoantibody activity with host polysialic acid. Although there is no direct evidence that such antibodies are harmful, it will be a difficult task to prove that such a meningococcal B vaccine is safe to use in humans.