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Infection and Immunity, July 2001, p. 4698-4701, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4698-4701.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Synthetic Polysaccharide Type 3-Related Di-, Tri-, and Tetrasaccharide-CRM197 Conjugates Induce Protection against Streptococcus pneumoniae Type 3 in Mice

Barry Benaissa-Trouw,1,* Dirk J. Lefeber,2 Johannis P. Kamerling,2 Johannes F. G. Vliegenthart,2 Kees Kraaijeveld,1 and Harm Snippe1

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

Received 3 November 2000/Returned for modification 6 December 2000/Accepted 29 March 2001

Di-, tri-, and tetrasaccharides, synthesized according to the chemical structure of pneumococcal polysaccharide type 3 (PS3), were coupled to the cross-reactive material (CRM197) of modified diphtheria toxin in different molar carbohydrate/protein ratios using the squarate coupling method. To study protective immunity, female BALB/c mice were subcutaneously immunized twice (with a 3-week interval) using the amount of conjugates corresponding to 2.5 µg of oligosaccharide per mouse. The conjugates evoked PS3 binding immunoglobulin G antibodies that lasted for at least 7 weeks after the booster. Immunogenicity was not influenced by the carbohydrate/protein ratio. All mice with PS3-specific antibodies survived the intraperitoneal challenge with Streptococcus pneumoniae type 3. Therefore, synthetic oligosaccharide-protein conjugates might have potential as vaccines.

* Corresponding author. Mailing address: Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, Vaccines Section, Utrecht Medical Center, HP G 04.614, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Phone: 31-30-2507635. Fax: 31-30-2541770. E-mail: B.J.BenaissaTrouw{at}lab.azu.nl.

Infection and Immunity, July 2001, p. 4698-4701, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4698-4701.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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