NEONATAL MOUSE PROTECTION AGAINST INFECTION WITH MULTIPLE GROUP-B STREPTOCOCCAL (GBS) SEROTYPES BY MATERNAL IMMUNIZATION WITH A TETRAVALENTGBS POLYSACCHARIDE-TETANUS TOROID CONJUGATE VACCINE

Most cases of neonatal sepsis and meningitis caused by group B strepto cocci (GBS) are attributable to one of four major capsular serotypes: Ia, Ib, II, or III, Because resistance to infection with GBS has been correlated with the presence of serum antibodies to the type-specific capsular polysaccharides in both experimental animals and human neonat es, efforts have been made to elicit protective immunity with GBS caps ular polysaccharide vaccines. However, the GBS capsular polysaccharide s alone are not highly immunogenic in either animals or human voluntee rs. Therefore, we and other investigators have attempted to enhance im munogenicity by coupling individual capsular polysaccharides to a carr ier protein. Here we report the synthesis and immunogenicity in rabbit s of a GBS type Ib polysaccharide-tetanus toroid vaccine prepared by t he direct, covalent attachment of tetanus toroid to a selected number of sialic acid residues on the type-specific polysaccharide. In additi on, the Ib polysaccharide-tetanus toroid conjugate vaccine was combine d with similar tetanus toroid conjugates of GBS type Ia, II, and III p olysaccharides to form a tetravalent GBS conjugate vaccine. Protective efficacy of the GBS tetravalent conjugate vaccine was demonstrated in a mouse maternal immunization-neonatal challenge model of GBS infecti on. The results support testing in human subjects of a multivalent GBS conjugate vaccine of this design, with the eventual goal of protectin g newborns against GBS infection.