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Infection and Immunity, May 1999, p. 2491-2496, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Alpha C Protein as a Carrier for Type III Capsular Polysaccharide and as a Protective Protein in Group B Streptococcal Vaccines

Claudia Gravekamp,1 Dennis L. Kasper,1,2,3 Lawrence C. Paoletti,1 and Lawrence C. Madoff1,2,*

Channing Laboratory1 and Division of Infectious Disease,2 Brigham and Women's Hospital, and Departments of Medicine and Microbiology and Molecular Genetics,3 Harvard Medical School, Boston, Massachusetts 02115

Received 18 November 1998/Returned for modification 3 February 1999/Accepted 18 February 1999

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-alpha 9r conjugate vaccine) or to two-repeat alpha C protein (resulting in III-alpha 2r conjugate vaccine) by reductive amination. Initial experiments with the III-alpha 9r 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-alpha 2r vaccine. Female mice were immunized three times with 0.5, 5, or 20 µg 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 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.

* Corresponding author. Mailing address: Channing Laboratory, 181 Longwood Ave., Boston, MA 02115. Phone: (617) 525-2677. Fax: (617) 731-1541. E-mail: lmadoff{at}channing.harvard.edu.

Infection and Immunity, May 1999, p. 2491-2496, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.