Vaginal colonization is the single most important risk factor for transmission of group B Streptococcus (GBS) from mothers to neonates, resulting in neonatal sepsis and/or meningitis. The long-term goal of this study is to determine whether vaccine-induced serum antibody to type III GBS will be sufficient to prevent vaginal acquisition of type III GBS. This study is linked to Division of Microbiology and Infectious Diseases protocol 04-018. It is a randomized, double-blinded, comparative clinical trial among young (18-40 years old), non-pregnant, sexually active women who are not currently colonized vaginally or rectally with type III GBS, it will be conducted to evaluate the efficacy of a GBS type III-TT vaccine for prevention of type III GBS vaginal acquisition. The observation period for each patient will be 18 months following vaccination. The specific objectives are: enroll 600 women (previously screened within last 14 days in a GBS Screening Protocol) identified as GBS type III negative, vaginally and rectally; vaccinate 600 women randomized to a 1:1 ratio with 50 micrograms of type III GBS polysaccharide conjugated to tetanus toxoid (GBS III-TT) or licensed vaccine containing Tetanus and Diphtheria Toxoids adsorbed for adult use (Td); measure reactogenicity by subject report in a 7-day symptom diary and by 1-2 day follow-up telephone call; evaluate women at 1, 2, 4, 6, 8, 10, 12, 14, 16 and 18 months for serum antibody response. Blood will be obtained at each of these clinic follow-up visits and serum will be used to compare type III GBS specific antibody levels at baseline and follow-up; assess vaginal and rectal acquisition by GBS at months 1, 2, 4, 6, 8, 10, 12, 14, 16 and 18 months using specimens obtained at the clinic visits; compare women receiving GBS III-TT vaccine to women receiving Td vaccine with respect to the time to first vaginal culture positive for type III GBS; assess the relationship between person-level covariates, including features of the decrease of type III GBS antibody levels over time, and the time to first vaginal culture positive for type III GBS; and assess the effect of vaginal colonization by hydrogen peroxide (H2O2)-producing Lactobacillus, sexual activity, antibiotic usage, rectal colonization with GBS and demographic features as risk factors for acquisition of type III GBS, independent of serum antibody levels. The primary study endpoint will be the time to the first vaginal swab that is type III GBS culture positive, with all previous cultures negative for type III GBS, not just the immediately preceding culture. The secondary endpoints include: the proportion of vaginal swabs that are type III GBS culture positive; the proportion of subjects whose vaginal cultures are type III GBS culture negative throughout the study; the frequency of vaginal colonization with GBS serotypes Ia, Ib, II and V; the measurement of serum immunoglobulin (Ig)G antibody levels to type III GBS at 1, 2, 4, 6, 8, 10 12, 14, 16 and 18 months following vaccination; the measurement of post-vaccination antibody levels to type III GBS, stratified by pre-vaccination levels of native antibody; the frequency of local and systemic symptoms attributable to vaccination; and the density of type III GBS cultured from vaginal swabs at culture positive visits.
