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Infection and Immunity, February 2001, p. 787-793, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.787-793.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Wouter T. M. Jansen,1,* Sietske Hogenboom,1 Mark J. L. Thijssen,2 Johannis P. Kamerling,2 Johannes F. G. Vliegenthart,2 Jan Verhoef,1 Harm Snippe,1 and André F. M. Verheul1,dagger

Vaccines Section, Eijkman-Winkler Institute for Microbiology, Infectious Diseases, and Inflammation, Utrecht University Hospital, 3584 CX Utrecht,1 and Department of Bio-Organic Chemistry, Bijvoet Center, Utrecht University, 3584 CH Utrecht,2 The Netherlands

Received 8 August 2000/Returned for modification 6 September 2000/Accepted 31 October 2000

The immunogenicity and protective capacity of Streptococcus pneumoniae 6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-P-), trisaccharide (ribitol-P-Gal-Glc-), and tetrasaccharide (Rha-ribitol-P-Gal-Glc-)-protein conjugates in rabbits and mice were studied. In rabbits, all saccharides conjugated to keyhole limpet hemocyanin (KLH) evoked high levels of pneumococcal (Pn) type 6B antibodies that facilitated type-specific phagocytosis. Unlike the disaccharide rabbit antisera, tri- and tetrasaccharide rabbit antisera also reacted with 6A PS in an enzyme-linked immunosorbent assay (ELISA) and promoted phagocytosis of 6A pneumococci. All these rabbit antisera passively protected mice against a Pn 6B challenge. The disaccharide conjugate-induced antiserum, however, failed to protect mice against a 6A challenge. In mice, phagocytic and protective anti-Pn 6B antibodies were only induced by the tetrasaccharide conjugate and not by PS 6B or PS 6B-protein conjugates. These antibodies did not cross-react with 6A PS in ELISA and were unable to phagocytize 6A pneumococci. In conclusion, the disaccharide and tetrasaccharide conjugates already contain epitopes capable of inducing 6B-specific, fully protective antibodies in rabbits and mice, respectively.

* Corresponding author. Present address: GBF, Section Microbiology D209, D-38124 Braunschweig, Germany. Phone: 0049 531 6181706. Fax: 0049 531 6181708. E-mail: JWO{at}GBF.de.

dagger Present address: Intervet International, Boxmeer, The Netherlands.

Infection and Immunity, February 2001, p. 787-793, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.787-793.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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