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 Laferriere, C. A.
Right arrow Articles by Jennings, H. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laferriere, C. A.
Right arrow Articles by Jennings, H. J.

 Previous Article  |  Next Article 

Infect Immun, June 1998, p. 2441-2446, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Streptococcus pneumoniae Type 14 Polysaccharide-Conjugate Vaccines: Length Stabilization of Opsonophagocytic Conformational Polysaccharide Epitopesdagger

Craig A. Laferriere, Ramesh K. Sood, Jean-Marc de Muys, Francis Michon, and Harold J. Jennings*

Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6

Received 3 November 1997/Returned for modification 12 January 1998/Accepted 16 March 1998

A simple and convenient method was developed for the preparation of Streptococcus pneumoniae type 14 polysaccharide (Pn14PS)-tetanus toxoid (TT) conjugate vaccines, using terminally linked Pn14PS fragments of different lengths. Native Pn14PS was simultaneously depolymerized and activated for conjugation by partial N-deacetylation followed by nitrous acid deamination which yielded fragments (1.4 to 150.0 kDa) having a free aldehyde at the reducing end. These were then conjugated to TT through their terminal aldehydic groups, using the reductive amination procedure. All of the above conjugates, when injected in rabbits, induced anti-Pn14PS antibodies, whereas the native Pn14PS did not. The amounts of anti-Pn14PS antibodies elicited by these conjugates, as determined by enzyme-linked immunosorbent assay, followed a trend with conjugates containing the highest-molecular-weight Pn14PS eliciting the highest titers. The same trend was also observed in the ability of the antibodies to opsonize and kill live type 14 pneumococci, although the increase in opsonophagocytic activity was more pronounced and did not correlate linearly with increases in antibody titer. Competitive inhibition of the binding of different conjugate antisera to the native Pn14PS, using Pn14PS fragments as inhibitors, established that the conjugates induced antibodies with specificities for different lengths of Pn14PS beginning at 2 repeating units (RU). It was also established, both immunologically and antigenically, that at least 4 RU of Pn14PS were required to form an extended conformational epitope and that approximately 22 RU of Pn14PS were required to duplicate the same epitope on the same saccharide chain. The conformational epitope was found to be essential for the induction of antibodies with high opsonophagocytic activity and that augmentation of opsonophagocytic activity was also dependent on further chain extension.

* Corresponding author. Mailing address: Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6. Phone: (613) 990-0821. Fax: (613) 941-1327. E-mail: Harry.Jennings{at}nrc.ca.

dagger National Research Council of Canada publication no. 39583.

Infect Immun, June 1998, p. 2441-2446, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Harris, S. L., Fernsten, P. (2009). Thermodynamics and Density of Binding of a Panel of Antibodies to High-Molecular-Weight Capsular Polysaccharides. CVI 16: 37-42 [Abstract] [Full Text]  
  • Safari, D., Dekker, H. A. T., Joosten, J. A. F., Michalik, D., de Souza, A. C., Adamo, R., Lahmann, M., Sundgren, A., Oscarson, S., Kamerling, J. P., Snippe, H. (2008). Identification of the Smallest Structure Capable of Evoking Opsonophagocytic Antibodies against Streptococcus pneumoniae Type 14. Infect. Immun. 76: 4615-4623 [Abstract] [Full Text]  
  • Yu, S., Xie, H., Datta, A., Naidu, N., Gu, X.-X. (2008). Galactose Residues on the Lipooligosaccharide of Moraxella catarrhalis 26404 Form the Epitope Recognized by the Bactericidal Antiserum from Conjugate Vaccination. Infect. Immun. 76: 4251-4258 [Abstract] [Full Text]  
  • Vulliez-Le Normand, B., Saul, F. A., Phalipon, A., Belot, F., Guerreiro, C., Mulard, L. A., Bentley, G. A. (2008). Structures of synthetic O-antigen fragments from serotype 2a Shigella flexneri in complex with a protective monoclonal antibody. Proc. Natl. Acad. Sci. USA 105: 9976-9981 [Abstract] [Full Text]  
  • Nierop Groot, M. N., Godefrooij, J., Kleerebezem, M. (2008). Heterologous Expression of the Pneumococcal Serotype 14 Polysaccharide in Lactococcus lactis Requires Lactococcal epsABC Regulatory Genes. Appl. Environ. Microbiol. 74: 912-915 [Abstract] [Full Text]  
  • Theilacker, C., Kaczynski, Z., Kropec, A., Fabretti, F., Sange, T., Holst, O., Huebner, J. (2006). Opsonic Antibodies to Enterococcus faecalis Strain 12030 Are Directed against Lipoteichoic Acid.. Infect. Immun. 74: 5703-5712 [Abstract] [Full Text]  
  • Michon, F., Uitz, C., Sarkar, A., D'Ambra, A. J., Laude-Sharp, M., Moore, S., Fusco, P. C. (2006). Group B Streptococcal Type II and III Conjugate Vaccines: Physicochemical Properties That Influence Immunogenicity.. CVI 13: 936-943 [Abstract] [Full Text]  
  • Kubler-Kielb, J., Liu, T.-Y., Mocca, C., Majadly, F., Robbins, J. B., Schneerson, R. (2006). Additional Conjugation Methods and Immunogenicity of Bacillus anthracis Poly-{gamma}-D-Glutamic Acid-Protein Conjugates.. Infect. Immun. 74: 4744-4749 [Abstract] [Full Text]  
  • Theilacker, C., Coleman, F. T., Mueschenborn, S., Llosa, N., Grout, M., Pier, G. B. (2003). Construction and Characterization of a Pseudomonas aeruginosa Mucoid Exopolysaccharide-Alginate Conjugate Vaccine. Infect. Immun. 71: 3875-3884 [Abstract] [Full Text]  
  • Mawas, F., Niggemann, J., Jones, C., Corbel, M. J., Kamerling, J. P., Vliegenthart, J. F. G. (2002). Immunogenicity in a Mouse Model of a Conjugate Vaccine Made with a Synthetic Single Repeating Unit of Type 14 Pneumococcal Polysaccharide Coupled to CRM197. Infect. Immun. 70: 5107-5114 [Abstract] [Full Text]  
  • Jansen, W. T. M., Hogenboom, S., Thijssen, M. J. L., Kamerling, J. P., Vliegenthart, J. F. G., Verhoef, J., Snippe, H., Verheul, A. F. M. (2001). Synthetic 6B Di-, Tri-, and Tetrasaccharide-Protein Conjugates Contain Pneumococcal Type 6A and 6B Common and 6B- Specific Epitopes That Elicit Protective Antibodies in Mice. Infect. Immun. 69: 787-793 [Abstract] [Full Text]  
  • Zou, W., Mackenzie, R., Therien, L., Hirama, T., Yang, Q., Gidney, M. A., Jennings, H. J. (1999). Conformational Epitope of the Type III Group B Streptococcus Capsular Polysaccharide. J. Immunol. 163: 820-825 [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»