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Infection and Immunity, September 2002, p. 5107-5114, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5107-5114.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Immunogenicity in a Mouse Model of a Conjugate Vaccine Made with a Synthetic Single Repeating Unit of Type 14 Pneumococcal Polysaccharide Coupled to CRM197

Fatme Mawas,1* Jutta Niggemann,2,{dagger} Christopher Jones,3 Michael J. Corbel,1 Johannis P. Kamerling,2 and Johannes F. G. Vliegenthart2

Division of Bacteriology,1 Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts EN6 3QG, United Kingdom,3 Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, NL-3508 TB Utrecht, The Netherlands2

Received 16 January 2002/ Returned for modification 29 April 2002/ Accepted 29 May 2002

Oligosaccharides (OSs) related to the pneumococcal type 14 capsular polysaccharide (Pn14PS) were studied for their ability to inhibit the binding between anti-PS14 antisera and native PS14. A synthetic tetrasaccharide corresponding to the repeating unit of the Pn14PS, a hexasaccharide mimic, and an octasaccharide fragment obtained by Pn14PS depolymerization were good inhibitors. CRM197 conjugates of the tetrasaccharide and an octasaccharide mimic were prepared by using either adipic acid diester or diethyl squarate linkers. The conjugate with the tetrasaccharide chains induced anti-Pn14PS antibodies when injected subcutaneously into mice, as determined by an enzyme-linked immunosorbent assay, and antibody titers increased with oligosaccharide loading. The adipic acid-linked tetrasaccharide conjugates elicited higher antibody titers than those prepared with a squarate spacer. The lower anti-Pn14PS antibody response of the octasaccharide mimic conjugate indicates the importance of the backbone galactose residue for an appropriate antibody response. The OS-CRM197 conjugate prepared from a single repeat unit of the Pn14PS is a potential vaccine candidate.


* Corresponding author. Mailing address: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, United Kingdom. Phone: 44-1707-654753, ext. 434. Fax: 44-707-663796. E-mail: fmawas{at}nibsc.ac.uk.

Editor: E. I. Tuomanen

{dagger} Present address: Abteilung Naturstoffchemie, Gesellschaft für Biotechnologische Forschung mbH, D-38124 Braunschweig, Germany.


Infection and Immunity, September 2002, p. 5107-5114, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5107-5114.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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