Human immune responses to polysaccharide antigens: an analysis of bacterial polysaccharide vaccines in infants.

Mechanisms of human immunity to polysaccharide encapsulated bacteria and the development and testing of the currently available purified polysaccharide bacterial vaccines are reviewed. These vaccines appear to be poorly immunogenic in infants under the age of two years--those at greatest risk for infection. In an effort to understand the poor responses of infants, the human immune response to polysaccharide antigens was characterized in more detail. Using pneumococcal polysaccharide type 3 as an example, it appears that human polysaccharide antibody responses are analogous to the type 2 T cell independent responses defined in the murine system. These studies suggest that the deficient polysaccharide response of human infants is due to a deficiency in maturation of distinct B lymphocyte subpopulations, as well as imbalanced T regulatory influences. The development of vaccines containing the purified capsular polysaccharides of S. pneumoniae, H.influenzae, and N. meningitidis during the past decade offered promise for the prevention of the major causes of bacterial sepsis and meningitis during childhood. The fulfillment of that promise was thwarted by the unrecognized complexities of human antibody responses to polysaccharide antigens. Continued vigorous research in this area has led us to a better understanding of the cellular requirements and immunoregulation of human polysaccharide antibody responses and has given us a clear direction for the pursuit of an effective means for immunization of infants.