Serotype specific and age dependent generation of pneumococcal polysaccharide specific memory B cells and antibody in response to immunization with a pneumococcal conjugate vaccine

University of Oxford, Dept. of Paediatrics, Oxford, Oxfordshire, UK; Edward Jenner Institute for Vaccine Research, Compton, Berkshire, UK

^* To whom correspondence should be addressed. Email: elizabeth.clutterbuck{at}paediatrics.ox.ac.uk.

	Abstract

Glycoconjugate vaccines have dramatically reduced 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.

Adults and 12-month old toddlers received a pneumococcal conjugate vaccine. Toddlers received a second dose at 14-months of age. Frequencies of diphtheria and serotypes 4, 14 and 23F polysaccharide specific plasma cells and memory B cells were determined by ELISPOT.

Toddlers had no pre-existing polysaccharide specific memory B-cells or serum IgG antibody, but good diphtheria specific memory responses. Plasma cell and memory B cell frequency increased by day 7 (p=<0.0001) in adults and toddlers following a single dose of conjugate, but polysaccharide responses were significantly lower in toddlers than adults (p=0.009 to <0.001). IgM dominated toddler antibody responses and class switching to IgG was serotype dependent. A second dose of vaccine enhanced antibody and memory B cell responses in toddlers but not the ex vivo plasma cell response.

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.