The kinetics and phenotype of the human B‐cell response following immunization with a heptavalent pneumococcal‐CRM₁₉₇ conjugate vaccine

Abstract

Summary Primary immunization of infants with protein–polysaccharide conjugate vaccines induces antipolysaccharide antibody and is highly effective in preventing invasive disease caused by encapsulated bacteria. However, recent experience from the UK indicates that this immunity is not sustained in the absence of booster doses of vaccine. This study aimed to establish the kinetics and phenotype of B‐cell subpopulations responding to booster immunization with a heptavalent pneumococcal conjugate vaccine (Pnc7), which is to be introduced into the primary immunization schedule in the UK during 2006. Six adult volunteers received a booster dose of Pnc7 12–18 months after primary immunization. CD27hi CD38hi CD20+/– IgG antibody‐forming cells were detected in peripheral blood with maximum frequency at days 6–7 after immunization. This was accompanied by a more prolonged rise in memory B cells that required in vitro stimulation with Staphylococcus aureus Cowan strain and interleukin‐2 to induce antibody secretion. These data provide evidence for at least two subsets of antibody‐forming cells involved in the secondary humoral response to a glycoconjugate vaccine in primed individuals. A briefly circulating subset of B cells that spontaneously secrete immunoglobulin G may be responsible for early defence against re‐encountered encapsulated bacteria. However, the kinetics of the appearance of these cells may indicate that the humoral immune response is too slow in defence against an organism that invades within days of acquisition. The more sustained presence of a memory population may provide persistence of antipolysaccharide antibody after a booster dose of vaccine and may also include re‐circulatory populations responsible for further anamnestic responses.

B Cell Memory to a Serogroup C Meningococcal Conjugate Vaccine in Childhood and Response to Booster: Little Association with Serum IgG Antibody

“…Memory B cells have been consistently shown to increase in frequency in the circulation following immunization (23,27,29,39), when newly generated Ag-specific memory B cells may be transiting through the circulation to other lymphoid tissues. Following a booster, Ag-specific memory B cells are detected at the end of the first week and are persistent for at least 1 mo (28,29,39). Following the Hib-MenC booster immunization, almost all children showed robust memory B cell responses, evidence of immune memory to priming MenC conjugate vaccine.…”

“…Hence, the measurement of Ag-specific plasma cells is possible during a limited window following immunization. Plasma cells in primed individuals are seen as early as day 4, peak by day 6-7, and are not detectable by day 12 following immunization (29,39,42). This window represents the period of migration of newly generated plasma cells (derived from Ag-specific activation of naive B cells that have proliferated and differentiated into Ag-specific ASC) from the germinal centers of lymphoid tissues to the bone marrow and mature plasma cells (derived from pre-existing Ag-specific memory B cells generated at priming that have differentiated and proliferated) and released into the circulation to secrete Ab.…”

“…Plasma cells are not detectable in peripheral blood at steady state (29,39). They are thought to reside predominantly in the bone marrow (40,41).…”

Polysaccharide-specific B cell responses to vaccination in humans

“…This technique involves measurement of the frequency of antibody-secreting cells in peripheral blood which spontaneously produce antibody. 6 In the steady-state, antigen-specific PCs in the peripheral blood are only present at a very low overall frequency in comparison to the total B cell population, but rise transiently following vaccination. PC kinetics following primary vaccination have been investigated in children after the first and third dose of a 3 dose schedule of meningococcal serogroup C conjugate vaccine at 2, 3, and 4 mo of age (MenCCV).…”

“…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] …”