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 Michon, F.
Right arrow Articles by Fusco, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Michon, F.
Right arrow Articles by Fusco, P. C.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, August 2006, p. 936-943, Vol. 13, No. 8
1071-412X/06/$08.00+0     doi:10.1128/CVI.00122-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Group B Streptococcal Type II and III Conjugate Vaccines: Physicochemical Properties That Influence Immunogenicity

Francis Michon, Catherine Uitz,{dagger} Arun Sarkar,{ddagger} Anello J. D'Ambra,§ Maryline Laude-Sharp, Samuel Moore,* and Peter C. Fusco

BioVeris Corporation, Gaithersburg, Maryland 20877

Received 30 March 2006/ Returned for modification 16 May 2006/ Accepted 30 May 2006

Recent efforts toward developing vaccines against group B streptococci (GBS) have focused on increasing the immunogenicity of GBS polysaccharides by conjugation to carrier proteins. However, partial depolymerization of GBS polysaccharides for the production of vaccines is a difficult task because of their acid-labile, antigenically critical sialic acids. Here we report a method for the partial depolymerization of type II and III polysaccharides by mild deaminative cleavage to antigenic fragments with reducing-terminal 2,5-anhydro-D-mannose residues. Through the free aldehydes of their newly formed end groups, the fragments were conjugated to tetanus toxoid by reductive amination. The resulting conjugates stimulated the production in animals of high-titer type II- and III-specific antibodies which induced opsonophagocytic killing of type II and III strains of group B streptococci. For the type II conjugates, immunogenicity increased as oligosaccharide size decreased, whereas for type III conjugates, the size of the oligosaccharides did not significantly influence immunogenicity. When oligosaccharides of defined size were conjugated through sialic acid residues, the resulting cross-linkages were shown to affect immunogenicity. When oligosaccharides were conjugated through terminal aldehyde groups generated by deamination, modification of the exocyclic chain of sialic acid did not influence immunogenicity.

* Corresponding author. Mailing address: Department of Vaccine Research, BioVeris Corporation, Gaithersburg, MD 20877. Phone: (301) 869-9800. Fax: (301) 947-5312. E-mail: smoore{at}bioveris.com.

{dagger} Present address: NABI, Research and Development, 12276 Wilkins Avenue, Rockville, MD 20852.

{ddagger} Present address: Glycomimetics, 101 Orchard Drive, Gaithersburg, MD 20878.

§ Present address: Novartis Knowledge Center, East Hanover, NJ 07936.

Clinical and Vaccine Immunology, August 2006, p. 936-943, Vol. 13, No. 8
1071-412X/06/$08.00+0     doi:10.1128/CVI.00122-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Moore, S., Farley, E. K., Fusco, P. C., Michon, F. (2007). Specificity of the Immune Response to a Modified Group B Meningococcal Polysaccharide Conjugate Vaccine. CVI 14: 106-109 [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»