The antibody responses of adult humans to certain polysaccharide antigens appear to be restricted to the IgG2 subclass. However, comparable data are not available from children; nor is it known what effect, if any, the presence of an adjuvant or a carrier protein may have on the subclass responses to a polysaccharide. The purposes of the proposed studies are: 1) to establish the normal immune responses of infants, children and adults to immunization with polysaccharides presented to the host with or without adjuvants, or as haptens, thus potentially affecting different immune mechanisms (for example, T-dependent vs T-independent); and 2) to determine whether immune response genes regulate human antibody responses to bacterial polysaccharides. We propose to determine the class and subclass (IgG1 and IgG2) serum antibody responses of subjects of different ages immunized with one of three experimental Haemophilus influenzae type b (Hib) vaccines: Purified type b capsule (PRP), PRP mixed with pertussis, and PRP covalently coupled to a protein carrier; and with Meningococcal A/C vaccine. Antipolysaccharide antibodies will be measured by ELISA. For measurement of subclass antibodies, we will employ highly sensitive and specific anti-subclass reagents prepared locally, and coupled to biotin. Most of the subjects participating in these vaccine trials already have been immunized and have been typed for HLA-A, HLA-B and HLA-DR, as well as for Gm and Km allotypes (genetic """"""""markers"""""""" on immunoglobulin molecules). The exception is black children in whom an immunogenicity trial with a new PRP-protein conjugate vaccine will be performed. Genes associated with certain markers, especially Km(1) in blacks, previously have been implicated in regulation of immune responses to PRP and in susceptibility to Hib diseases. Therefore, we will be able to search for associations between specific antibody responses to vaccine, and the presence or absence of Km(1) or other markers. The above studies are being conducted in an outbred population. We also propose to measure the antibody responses of members of an inbred Amish population recently immunized with PRP and Meningococcal A/C vaccines. In this population, individuals sharing a haplotype will do so by descent, and therefore share the same linked genes. The results of these studies may provide unambiguous documentation of the existence of genetic regulation of immune responses in humans, and will contribute to a better understanding of the immune responses of children to several important bacterial polysaccharide vaccines.
Showing the most recent 10 out of 61 publications
