Alpha C protein as a carrier for type III capsular polysaccharide and as aprotective protein in group B streptococcal vaccines

The alpha C protein, a protective surface protein of group B streptococci ( GBS), is present in most non-type III GBS strains. Conjugate vaccines compo sed of the alpha C protein and type III capsular polysaccharide (CPS) might be protective against most GBS infections. In this study, the type III CPS was covalently coupled to full-length, nine-repeat alpha C protein (result ing in III-alpha 9r conjugate vaccine) or to two-repeat alpha C protein (re sulting in III-alpha 2r conjugate vaccine) by reductive amination, Initial experiments with the III-alpha 9r vaccine showed that it was poorly immunog enic in mice with respect to both vaccine antigens and was suboptimally eff icacious in providing protection in mice against challenge with GBS, Theref ore, modified vaccination protocols were used with the III-alpha 2r vaccine . Female mice were immunized three times with 0.5, 5, or 20 mu g of the III -alpha 2r vaccine with an aluminum hydroxide adjuvant and bred. Ninety-five percent of neonatal mice born to dams immunized with the III-alpha 2r vacc ine survived challenge with GBS expressing type III CPS, and 60% survived c hallenge with GBS expressing wild-type (nine-repeat) alpha C protein; 18 an d 17%, respectively, of mice in the negative control groups survived (P, <0 .0001). These protection levels did not differ significantly from those obt ained with the type III CPS-tetanus toroid conjugate vaccine and the unconj ugated two repeat alpha C protein, which protected 98 and 58% of neonates f rom infection with GBS expressing type III CPS or the alpha C protein, resp ectively. Thus, the two-repeat alpha C protein in the vaccine was immunogen ic and simultaneously enhanced the immunogenicity of type III CPS, III-alph a vaccines may be alternatives to GBS polysaccharide-tetanus toroid vaccine s, eliciting additional antibodies protective against GBS infection.