title: Alpha C protein as a carrier for type III capsular polysaccharide and as a protective protein in group B streptococcal vaccines.
abstract: The alpha C protein, a protective surface protein of group B streptococci (GBS), is present in most non-type III GBS strains. Conjugate vaccines composed 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 (resulting in III-alpha9r conjugate vaccine) or to two-repeat alpha C protein (resulting in III-alpha2r conjugate vaccine) by reductive amination. Initial experiments with the III-alpha9r vaccine showed that it was poorly immunogenic in mice with respect to both vaccine antigens and was suboptimally efficacious in providing protection in mice against challenge with GBS. Therefore, modified vaccination protocols were used with the III-alpha2r vaccine. Female mice were immunized three times with 0.5, 5, or 20 microgram of the III-alpha2r vaccine with an aluminum hydroxide adjuvant and bred. Ninety-five percent of neonatal mice born to dams immunized with the III-alpha2r vaccine survived challenge with GBS expressing type III CPS, and 60% survived challenge with GBS expressing wild-type (nine-repeat) alpha C protein; 18 and 17%, respectively, of mice in the negative control groups survived (P, <0.0001). These protection levels did not differ significantly from those obtained with the type III CPS-tetanus toxoid conjugate vaccine and the unconjugated two-repeat alpha C protein, which protected 98 and 58% of neonates from infection with GBS expressing type III CPS or the alpha C protein, respectively. Thus, the two-repeat alpha C protein in the vaccine was immunogenic and simultaneously enhanced the immunogenicity of type III CPS. III-alpha vaccines may be alternatives to GBS polysaccharide-tetanus toxoid vaccines, eliciting additional antibodies protective against GBS infection.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gravekamp
authors.forename: D L
authors.initials: DL
authors.lastname: Kasper
authors.forename: L C
authors.initials: LC
authors.lastname: Paoletti
authors.forename: L C
authors.initials: LC
authors.lastname: Madoff
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D016667:Bacterial Capsules; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007116:Immunization, Passive; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D011247:Pregnancy; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control; D022541:Streptococcal Vaccines; D013292:Streptococcus agalactiae / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D011135:Polysaccharides, Bacterial; D022541:Streptococcal Vaccines; D018074:Vaccines, Conjugate; C105866:group B streptococcal type III capsular polysaccharide-tetanus toxoid vaccine; C032263:streptococcal polysaccharide type III group B