IMMUNE-RESPONSE TO TYPE-III GROUP-B STREPTOCOCCAL POLYSACCHARIDE-TETANUS TOXOID CONJUGATE VACCINE

Group B Streptococcus (GBS) is an important perinatal pathogen, Becaus e transplacentally acquired maternal antibodies to the GBS capsular po lysaccharides (CPS) confer protection, prevention of infant disease ma y be possible after immunization of women. Unfortunately, the purified CPS of GBS are only variably immunogenic in adults; therefore to enha nce immunogenicity we have designed and developed a CPS-protein conjug ate vaccine. The lability of a conformationally dependent epitope on t he III CPS containing a critical sialic acid residue was important to consider in vaccine design, 100 women were randomized to receive GBS t ype III CPS-tetanus toroid conjugate (III-TT) vaccine at one of three doses; unconjugated GBS type III CPS; or saline, Serum samples were ob tained before immunization and 2, 4, 8, and 26 wk thereafter, and spec ific antibody to type III CPS was measured. Vaccines were well tolerat ed. In sera from recipients of the highest dose of III-TT, CPS-specifi c IgG levels rose from a geometric mean of 0.09 mu g/ml before immuniz ation to 4.53 mu g/ml 8 wk later, whereas levels in recipients of unco njugated type III CPS rose from 0.21 mu g/ml to 1.41 mu g/ml. Lower do ses resulted in lower antibody levels, A greater than or equal to 4-fo ld rise in antibody concentration was achieved in 90% of recipients of III-TT compared with 50% of those that received III CPS (P = 0.0015), Antibodies evoked by the conjugate vaccine recognized a conformationa lly dependent epitope of the III-CPS, promoted opsonophagocytosis and killing of GBS, and, after maternal immunization, protected neonatal m ice from lethal challenge with type III GBS, We conclude that directed coupling of type III GBS polysaccharide to a carrier protein yielded a conjugate vaccine with preserved expression of a highly labile confo rmational epitope involving sialic acid and enhanced immunogenicity co mpared with uncoupled CPS.