The objective of this proposal is to assess by case-control methods the protective efficacy characteristics of Haemophilus influenzae type b (Hib) conjugate vaccines to be licensed by 1991 for routine immunization of infants 2 to 6 months of age. Further, to characterize in detail the repertoire of antibodies induced by each of the candidate vaccines (PRP-D, HbOC, PRP-OMP, PRP-T) after a primary dose, one and two booster doses, and in sera obtained a year after immunization, so that correlations can be made between immunologic determinants and protective efficacy. The efficacy of the vaccines will be determined throughout Los Angeles County (population 8.5 million), where we have established a detailed and complete surveillance system. AN Hib cases will be carefully investigated to ascertain immunization histories, collect detailed epidemiologic risk factor information and assess potential confounders for vaccine efficacy. Controls obtained by random digit telephone dialing will be matched for area of residence and age and similarly investigated. Efficacy will be characterized for each licensed vaccine, by age, by dose, by time after immunization and by population group. From 18 immunogenicity studies already completed, antibodies induced by each vaccine will be characterized for total antibody binding, isotype (IgG, IgM, IgA), IgG subclass (IgG1, IgG2), clonal diversity and typing of the light chain variable region. A better understanding of the immunologic determinants of protection in humans will be essential for the development of improved bacterial conjugate vaccines and for establishing optimal recommendations for Hib immunization.