The human B cell response to a pneumococcal conjugate vaccine.

The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine (Pnc7) has been introduced to target the major disease causing pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) in childhood where invasive pneumococcal disease remains a significant global cause of childhood mortality. The aim of this thesis was to address questions related to the pneumococcal capsular polysaccharide specific B cell response. One week after a single dose of Pnc7 vaccine it was possible to detect spontaneously secreting IgG plasma cells in the peripheral blood of 12 month old toddlers and young adults. The plasma cells were identified as either CD20+CD27+sIg+CD38+ or CD20-CD27+sIglo/-CD38+. Prior to immunisation memory B cells specific for pneumococcal capsular polysaccharides were present in 100% of young adults, but barely detectable in adults aged 47-65 years and were undetectable in toddlers. A single dose of Pnc7 induced elevated frequencies of IgG memory B cells in all age groups, but two doses were required in order to generate equivalent frequencies in adults and toddlers. The generation of IgG memory was dependent on age at time of immunisation and on the serotype polysaccharide. Generation of IgG memory requires previous natural exposure or immunisation to prime the immune system. Such exposure generates IgM memory in young children and enhancing IgM memory may be important for protection. The IgM response can be replaced by generation of a high avidity IgG response, enhance protection of the very young and elderly through immunisation