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Vaccine, Vol. 21 (13-14) (2003) pp. 1554-1559
© 2002 Elsevier Science Ltd. All rights reserved.
PII: S0264-410X(02)00675-8
 

Non-interference between two protein carriers when used with the same polysaccharide for pneumococcal conjugate vaccines in 2-year-old children

Porter Anderson, John Treanor, Susan Porcelli and Michael Pichichero * michael_pichichero@urmc.rochester.edu

Departments of Microbiology/Immunology, Medicine, and Pediatrics, Elmwood Pediatric Group, University of Rochester Medical Center, 601 Elmwood Avenue, P.O. Box 672, Rochester, NY 14642, USA

Received 2 May 2001; received in revised form 8 January 2002; accepted 18 January 2002

Abstract

The carriers tetanus toxoid (T) and diphtheria CRM-197 (C) were compared in conjugate vaccines using identical coupling chemistry and polysaccharide (PS) loading, for safety and immunogenicity in 2-year-old children. Also tested were a mixture of halved doses of both carriers bearing the same PS serotypes. For this study, PS types 6A, 14, 19F, and 23F (separately) were coupled to T or C by reductive amination at PS/protein ratios of 0.50±0.18. With each carrier the four PS types were combined, giving the tetravalent vaccines "T-6, -14, -19, -23" or "C-6, -14, -19, -23" containing 50µg of the carrier and roughly 20µg total PS per ml of saline (no adjuvant). The children received primary (1´) injections of 50µg (protein) of either vaccine or a mixture of 25µg of both; identical secondary (2´) injections were given 2 months afterwards. Sera were taken before the 1´ and 2´ and 1 month post-2´, and serum IgG responses to the four PS were determined by ELISA.

For geometric mean (GM) post-1´ antibody, "C-6, -14, -19, -23" exceeded "T-6, -14, -19, -23" for type 19F; for 2´ antibody, "T-6, -14, -19, -23" exceeded "C-6, -14, -19, -23" for type 14, but "C-6, -14, -19, -23" and the T/C mixture exceeded "T-6, -14, -19, -23" for the type 23F response. No other differences were significant. Analyzed by individual fold-rises, "C-6, -14, -19, -23" and the T/C mixture exceeded "T-6, -14, -19, -23" for types 19F and 23F. Thus, there was no consistent difference between the T and C carriers; rather, the results differed by serotype.

When a mixture of halved doses of "T-6, -14, -19, -23" and "C-6, -14, -19, -23" was injected, neither negative nor positive interference with the PS antibody responses was found. Anticipating multivalent PS conjugate vaccines of the future to be used in infancy, this strategy would have two hypothetical advantages worth further investigation--avoiding "carrier epitopic overload" by reducing each carrier dosage and recruiting T-helper activity by both carriers for each PS.

Keywords: Pneumococcal conjugate vaccines; Protein carriers; Vaccine interference; Carrier epitopic overload

*Corresponding author. Tel.: +1-716-275-1534; fax: +1-716-273-1289.

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© Copyright 2003, Elsevier Science, All rights reserved.

 

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