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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 Response¹

Geraldine Blanchard Rohner^2,*, Matthew D. Snape^*, Dominic F. Kelly^*, Tessa John^*, Anita Morant^*, Ly-Mee Yu, Astrid Borkowski, Francesca Ceddia^¶, Ray Borrow, Claire-Anne Siegrist^|| and Andrew J. Pollard^*

^* Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine and Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom; Vaccine Evaluation Unit, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester, United Kingdom; Novartis Vaccines and Diagnostics, Marburg, Germany; ^¶ Novartis Vaccines and Diagnostics, Siena, Italy; and ^|| Center of Vaccinology and Neonatal Immunology, University of Geneva, Geneva, Switzerland

Rapid waning of anti-polysaccharide bactericidal Ab and vaccine effectiveness is observed following infant immunization with the serogroup C meningococcal (MenC) glycoconjugate vaccine. This is despite the demonstrable presence of immunological memory. Persistence of functional Ab, therefore, appears to be the key determinant of MenC conjugate vaccine effectiveness. Ab persistence is thought to depend in the short term on the survival of plasma cells generated during priming and in the longer term on the production of new Ab secreting cells from memory B cells. In this study, we found a strong association between the level of MenC-specific Ab and the frequency of memory B cells measured at 5 mo of age (1 mo after 3-dose primary immunization with MenC conjugate vaccine), and the persistence of functional Ab at one year of age. These findings suggest that these two parameters are good markers of B cell responses to priming and can be used as predictors of long term humoral immunity induced by glycoconjugate vaccines received in early infancy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Novartis Vaccines. A.J.P. is a Jenner Institute Investigator.

² Address correspondence and reprint requests to Dr. Geraldine Blanchard Rohner, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, OX3 7LJ, U.K. E-mail address: geraldine.blanchard{at}paediatrics.ox.ac.uk

³ Abbreviations used in this paper: MenC, serogroup C meningococcal; MenCV, MenC conjugate vaccine; SBA, serum bactericidal activity; Hib, Haemophilus influenzae type b; PWM, Pokeweed mitogen; SAC, Staphylococcus aureus Cowan bacteria; ASC, Ab-secreting cells.

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