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

Abstract

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

Polysaccharide-specific B cell responses to vaccination in humans

“…A greater frequency of PCs is generated following the third dose of MenCCV than following the first, 8 although in toddlers receiving their first dose of pneumococcal conjugate vaccine at 12 mo of age, revaccination at 14 mo did not increase PC frequency in peripheral blood relative to the same time point (1 wk post-vaccination) at 12 mo. 10 Despite showing similar kinetics, there are differences in the number of plasma cells induced by plain polysaccharide and glycoconjugate vaccines. In adolescents receiving either a booster dose of MenCCV or MenCPS, both of which contained the same quantity of polysaccharide antigen, the PC response was of greater magnitude in the glycoconjugate group, although there were no differences in the timing of responses.…”

“…Twelve month old toddlers with little or no prior exposure to encapsulated bacteria required at least 2 doses of PCV-7 to reach B MEM frequencies equivalent to those following a single dose in adults. 10 However, all of the adults in this study already had detectable polysaccharide-specific B MEM at baseline, likely induced by prior pneumococcal colonization, in effect priming the immune system. Another study reported that age at primary vaccination (ranging between 6 mo and 34 y) with a glycoconjugate did not affect the induction and persistence of polysaccharide-specific B MEM .…”

“…This is because the majority of vaccine-naïve adults already have pre-existing immunity to capsular polysaccharides, which also serve as vaccine antigens. 10,13,14 This immunity, in the form of B MEM and serum antibody is probably acquired following repeated nasopharyngeal carriage of encapsulated bacteria. To overcome this problem, a novel T-dependent protein antigen for unvaccinated individuals in the UK, the rabies vaccine, was used to investigate B cell kinetics in a controlled setting of primary, secondary and tertiary immune responses.…”

“…In this manuscript we aim to describe the kinetics (timing of responses) and magnitude of both polysaccharide-specific plasma cell (PC) and memory B cell (B MEM ) responses following vaccination, summarizing data from previous studies in children, adolescents, and adults. [5][6][7][8][9][10][11][12][13] …”

Effect of cryopreservation of peripheral blood mononuclear cells (PBMCs) on the variability of an antigen-specific memory B cell ELISpot

“…27,28 PBMCs were first isolated from whole blood using lymphoprep™ (Axis-Shield Diagnostics) density gradient centrifugation. After a wash step, PBMCs were cultured at a concentration of 2 × 10 5 cells/well in a mixture of SAC (S. aureus Cowan strain, 1:5000, Calbiochem), CpG oligodeoxynucleotide 2006 (1.8 µg/mL, Source Bioscience) and pokeweed mitogen (PWM, 83 ng/ mL, Sigma) for 6 d at 37 °C, 5% CO 2 , and 95% humidity.…”