This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gravekamp, C.
Right arrow Articles by Madoff, L. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gravekamp, C.
Right arrow Articles by Madoff, L. C.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:

  • Yang, H.-H., Mascuch, S. J., Madoff, L. C., Paoletti, L. C. (2008). Recombinant Group B Streptococcus Alpha-Like Protein 3 Is an Effective Immunogen and Carrier Protein. CVI 15: 1035-1041 [Abstract] [Full Text]  
  • Seepersaud, R., Hanniffy, S. B., Mayne, P., Sizer, P., Le Page, R., Wells, J. M. (2005). Characterization of a Novel Leucine-Rich Repeat Protein Antigen from Group B Streptococci That Elicits Protective Immunity. Infect. Immun. 73: 1671-1683 [Abstract] [Full Text]  
  • Lindahl, G., Stalhammar-Carlemalm, M., Areschoug, T. (2005). Surface Proteins of Streptococcus agalactiae and Related Proteins in Other Bacterial Pathogens. Clin. Microbiol. Rev. 18: 102-127 [Abstract] [Full Text]  
  • Creti, R., Fabretti, F., Orefici, G., von Hunolstein, C. (2004). Multiplex PCR Assay for Direct Identification of Group B Streptococcal Alpha-Protein-Like Protein Genes. J. Clin. Microbiol. 42: 1326-1329 [Abstract] [Full Text]  
  • Cheng, Q., Debol, S., Lam, H., Eby, R., Edwards, L., Matsuka, Y., Olmsted, S. B., Cleary, P. P. (2002). Immunization with C5a Peptidase or Peptidase-Type III Polysaccharide Conjugate Vaccines Enhances Clearance of Group B Streptococci from Lungs of Infected Mice. Infect. Immun. 70: 6409-6415 [Abstract] [Full Text]  
  • Martin, D., Rioux, S., Gagnon, E., Boyer, M., Hamel, J., Charland, N., Brodeur, B. R. (2002). Protection from Group B Streptococcal Infection in Neonatal Mice by Maternal Immunization with Recombinant Sip Protein. Infect. Immun. 70: 4897-4901 [Abstract] [Full Text]  
  • Kong, F., Gowan, S., Martin, D., James, G., Gilbert, G. L. (2002). Molecular Profiles of Group B Streptococcal Surface Protein Antigen Genes: Relationship to Molecular Serotypes. J. Clin. Microbiol. 40: 620-626 [Abstract] [Full Text]  
  • Cheng, Q., Carlson, B., Pillai, S., Eby, R., Edwards, L., Olmsted, S. B., Cleary, P. (2001). Antibody against Surface-Bound C5a Peptidase Is Opsonic and Initiates Macrophage Killing of Group B Streptococci. Infect. Immun. 69: 2302-2308 [Abstract] [Full Text]  
  • Brodeur, B. R., Boyer, M., Charlebois, I., Hamel, J., Couture, F., Rioux, C. R., Martin, D. (2000). Identification of Group B Streptococcal Sip Protein, Which Elicits Cross-Protective Immunity. Infect. Immun. 68: 5610-5618 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»