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Infection and Immunity, September 1999, p. 4862-4869, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

B- and T-Cell Immune Responses to Pneumococcal Conjugate Vaccines: Divergence between Carrier- and Polysaccharide-Specific Immunogenicity

Tera L. McCool,1,2 Clifford V. Harding,2 Neil S. Greenspan,2,3,* and John R. Schreiber1,2,3,*

Department of Pediatrics1 and Institute of Pathology,2 Case Western Reserve University School of Medicine, and Rainbow Babies and Children's Hospital,3 Cleveland, Ohio 44106

Received 31 March 1999/Returned for modification 12 May 1999/Accepted 2 July 1999

Conjugation of various serotypes of pneumococcal polysaccharide (PnPS) to carrier protein enhances the magnitude of the polysaccharide-specific antibody response, presumably by eliciting T-cell help. However, variability in PnPS serotype-specific immunogenicity has been observed. CBA/J mice immunized with either 6B or 19F PnPS conjugated to the protein carrier Cross Reactive Material197 (CRM197) produce a strong anti-PnPS antibody response; however, when mice are immunized with 23F PnPS conjugated to CRM197, they fail to produce a significant anti-PnPS response. In order to determine whether this difference was related to alterations in antigen processing of the carrier protein and the subsequent T-cell responses, we studied proliferation of lymphocytes from CBA/J mice immunized with CRM197 alone or conjugated to 6B, 19F, or 23F PnPS. T-cell proliferative responses to synthetic peptides demonstrated that lymph node cells elicited by the poorly immunogenic conjugate 23F-CRM197 recognized many, but not all, of the epitopes recognized by lymph node cells elicited by 6B- and 19F-CRM197 as well as additional epitopes. Despite marked differences in PnPS-specific immunogenicity, all mice made high titers of CRM197 antibodies of the immunoglobulin G1 isotype. Cells from mice immunized with any of the conjugates yielded vigorous T-cell responses to whole antigen. We conclude that the serotype of PnPS can alter the peptide specificities of T-cell responses, but even a poorly immunogenic PnPS conjugate can elicit a significant T-cell response. Thus, conjugation of PnPS to a carrier protein that elicits carrier-specific T- and B-cell responses does not necessarily enhance PnPS immunogenicity.

* Corresponding author. Mailing address for John R. Schreiber: Division of Infectious Diseases, Rainbow Babies and Children's Hospital, 11100 Euclid Ave., Cleveland, OH 44106. Phone: (216) 844-3645. Fax: (216) 844-8362. E-mail: jrs3{at}po.cwru.edu. Mailing address for Neil S. Greenspan: Institute of Pathology, Biomedical Research Building, Rm. 927, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106. Phone: (216) 368-1280. Fax: (216) 368-1300. E-mail: nsg{at}po.cwru.edu.

Infection and Immunity, September 1999, p. 4862-4869, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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