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Clinical and Vaccine Immunology, February 2008, p. 182-193, Vol. 15, No. 2
1071-412X/08/$08.00+0     doi:10.1128/CVI.00336-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Serotype-Specific and Age-Dependent Generation of Pneumococcal Polysaccharide-Specific Memory B-Cell and Antibody Responses to Immunization with a Pneumococcal Conjugate Vaccine{triangledown}

Elizabeth A. Clutterbuck,1* Sarah Oh,1 Mainga Hamaluba,1 Sharon Westcar,1 Peter C. L. Beverley,2 and Andrew J. Pollard1

Department of Paediatrics, University of Oxford, Oxford, Oxfordshire, United Kingdom,1 Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom2

Received 14 August 2007/ Returned for modification 13 September 2007/ Accepted 12 November 2007

Glycoconjugate vaccines have dramatically reduced the incidence of encapsulated bacterial diseases in toddlers under 2 years of age, but vaccine-induced antibody levels in this age group wane rapidly. We immunized adults and 12-month-old toddlers with heptavalent pneumococcal conjugate vaccine to determine differences in B-cell and antibody responses. The adults and 12-month-old toddlers received a pneumococcal conjugate vaccine. The toddlers received a second dose at 14 months of age. The frequencies of diphtheria toxoid and serotype 4, 14, and 23F polysaccharide-specific plasma cells and memory B cells were determined by enzyme-linked immunospot assay. The toddlers had no preexisting polysaccharide-specific memory B cells or serum immunoglobulin G (IgG) antibody but had good diphtheria toxoid-specific memory responses. The frequencies of plasma cells and memory B cells increased by day 7 (P < 0.0001) in the adults and the toddlers following a single dose of conjugate, but the polysaccharide responses were significantly lower in the toddlers than in the adults (P = 0.009 to <0.001). IgM dominated the toddler antibody responses, and class switching to the IgG was serotype dependent. A second dose of vaccine enhanced the antibody and memory B-cell responses in the toddlers but not the ex vivo plasma cell responses. Two doses of pneumococcal conjugate vaccine are required in toddlers to generate memory B-cell frequencies and antibody class switching for each pneumococcal polysaccharide equivalent to that seen in adults.

* Corresponding author. Mailing address: Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, The Churchill Hospital, Oxford OX3 7LJ, United Kingdom. Phone: 44 (0)1865 857442. Fax: 44 (0)1865 857420. E-mail: elizabeth.clutterbuck{at}paediatrics.ox.ac.uk

{triangledown} Published ahead of print on 11 November 2007.

Clinical and Vaccine Immunology, February 2008, p. 182-193, Vol. 15, No. 2
1071-412X/08/$08.00+0     doi:10.1128/CVI.00336-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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