This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsai, T. F. Articles by Siegrist, C.-A. Search for Related Content PubMed PubMed Citation Articles by Tsai, T. F. Articles by Siegrist, C.-A.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, August 2006, p. 854-861, Vol. 13, No. 8
1071-412X/06/$08.00+0     doi:10.1128/CVI.00059-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Early Appearance of Bactericidal Antibodies after Polysaccharide Challenge of Toddlers Primed with a Group C Meningococcal Conjugate Vaccine: What Is Its Role in the Maintenance of Protection?

Theodore F. Tsai,^1, Ray Borrow,² Hanspeter E. Gnehm,³ Bernard Vaudaux,⁴ Ulrich Heininger,⁵ Daniel Desgrandchamps,⁶ Christoph Aebi,⁷ Paul Balmer,² Ronald D. Pedersen,¹ Bernard Fritzell,⁸ and Claire-Anne Siegrist^9*

Wyeth Research, 500 Arcola Rd., Collegeville, Pennsylvania 19426,¹ Vaccine Evaluation Department, Manchester Medical Microbiology Partnership, P.O. Box 209, Clinical Sciences Building, Manchester Royal Infirmary, Manchester, M13 9WZ, United Kingdom,² Department of Pediatrics, Kantonsspital Aarau AG, Tellstrasse, CH-5001 Aarau,³ Department of Paediatrics, University Hospital (CHUV & HEL), CH-1011 Lausanne/VD,⁴ University Children's Hospital (UKBB), Römergasse 8, CH-4058 Basel/BS,⁵ Department of Pediatrics, Children's Hospital of Lucerne, Lucerne,⁶ Department of Pediatrics and Institute for Infectious Diseases, Medizinische Universitäts-Kinderklinik, CH-3010 Bern/BE,⁷ Scientific Affairs, Wyeth Research, La Defense 4, 92931 Paris La Defense Cedex, France; and,⁸ Paediatric Department, Center for Vaccinology and Neonatal Immunology, University of Geneva, CMU, 1 Michel Servet, 1211 Geneva 4, Switzerland⁹

Received 14 February 2006/ Returned for modification 28 April 2006/ Accepted 23 May 2006

The contribution of memory responses after meningococcal vaccination to protection may depend on the rapidity of the response. Toddlers were challenged with a licensed polysaccharide (PS) vaccine 1 year after vaccination with a single dose of meningococcal group C-CRM₁₉₇ conjugate (MCC) vaccine at the age of 12 to 15 months. Bactericidal antibodies and immunoglobulin G (IgG) antibodies detected by an enzyme-linked immunosorbent assay (ELISA) were measured before challenge and 4, 7, 14, or 21 Days later ("Days" refer to treatment groups, "days" to sampling days). Among 281 subjects in the intent-to-treat population, 173 per-protocol (PP) subjects were challenged with 10 µg PS antigen and 103 others with a 50-µg PS vaccinating dose. Capsular PS-specific ELISA IgG titers were negligible in baseline samples and increased only twofold within 4 days of PS administration. In contrast, the proportion of PP subjects with serum bactericidal antibody (SBA) titers of 1:8 or 1:128 increased, respectively, from 41% and 16% before challenge to 84% and 74% at Day 4 and to 100% and 97% at Day 7. Recipients of 50 µg PS responded with similar kinetics but showed a trend toward higher antibody levels. Unexpectedly, 69% of subjects bled on days 2 to 3 already had achieved SBA titers of 1:8. The majority of toddlers previously immunized with MCC and challenged 1 year later with PS antigen mounted protective levels of bactericidal antibody within 2 to 4 days.

Present address: Novartis Vaccines and Diagnostics, Bell Atlantic Tower, 1717 Arch St., Philadelphia, PA 19103.

This article has been cited by other articles:

• Rohner, G. B., Snape, M. D., Kelly, D. F., John, T., Morant, A., Yu, L.-M., Borkowski, A., Ceddia, F., Borrow, R., Siegrist, C.-A., Pollard, A. J. (2008). The Magnitude of the Antibody and Memory B Cell Responses during Priming with a Protein-Polysaccharide Conjugate Vaccine in Human Infants Is Associated with the Persistence of Antibody and the Intensity of Booster Response. J. Immunol. 180: 2165-2173 [Abstract] [Full Text]