Most cases of
neonatal sepsis and
meningitis caused by group B streptococci (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 neonates, efforts have been made to elicit protective immunity with GBS capsular
polysaccharide vaccines. However, the GBS capsular
polysaccharides alone are not highly immunogenic in either animals or human volunteers. Therefore, we and other investigators have attempted to enhance immunogenicity by coupling individual capsular
polysaccharides to a
carrier protein. Here we report the synthesis and immunogenicity in rabbits of a GBS type Ib
polysaccharide-
tetanus toxoid vaccine prepared by the direct, covalent attachment of
tetanus toxoid to a selected number of
sialic acid residues on the type-specific
polysaccharide. In addition, the Ib
polysaccharide-
tetanus toxoid conjugate vaccine was combined with similar
tetanus toxoid conjugates of GBS type Ia, II, and III
polysaccharides 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
infection. The results support testing in human subjects of a multivalent GBS
conjugate vaccine of this design, with the eventual goal of protecting newborns against GBS
infection.