Vaccination‐Induced Circulation of Human B Cells Secreting Type‐Specific Antibodies against Pneumococcal Polysaccharides

Abstract

Indirect plaque-forming cell assays detecting B cells secreting antibodies against capsular pneumococcal polysaccharide (PPS) antigens are described. In healthy adult volunteers the total number of B cells secreting IgM antibodies against the antigens in a polyvalent PPS vaccine reached a maximum in the blood 6 days after in vivo immunization (mean: 552/10(6) mononuclear cells), whereas the highest concentration of IgG and IgA antibody-secreting cells (SC) were detected 7 days after immunization (means: 628 and 1691/10(6]. B cells secreting antibodies to PPS type 3 (PPS3), PPS8, PPS18C and C-polysaccharide (CPS)--a cell wall antigen common to all pneumococci--constituted 9%, 16%, 6% and 5% (means) of the total number of antibody SC respectively. While the majority of the anti-PPS-SC secreted IgA antibodies, the anti-CPS-SC almost exclusively secreted IgG. Pre-vaccination concentrations of anti-PPS were generally low in contrast to antibodies against CPS, which were present in high concentrations in all individuals. The discrepancy in the Ig class of the antibody SC is probably related to the difference in the pre-vaccination immunity against PPS and CPS.

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

“…These cells disappear from the circulation by day 9 of the vaccine response. A similar time course has also been reported in response to plain pneumococcal polysaccharide vaccines, tetanus toxoid, and influenza vaccines (17,25); and it is likely that these AFCs are plasma cells generated from preexisting memory cells. However, various subsets of B cells are presumed to circulate through the peripheral blood following immunization, including mature plasma cells, nonsecreting antigen-specific memory B cells, and long-lived plasma cell precursors migrating to the bone marrow (20,44); and uncertainty remains about which of these cell subsets is responsible for both the early rise in antibody levels after immunization and the prolonged production of antibody over the subsequent months and years.…”

Pandemic H1N1 Influenza Infection and Vaccination in Humans Induces Cross-Protective Antibodies that Target the Hemagglutinin Stem

“…First, we randomly cloned antibodies from newly generated plasmablasts (PB) circulating in the blood of recently infected patients. This approach was based upon observations that ∼7 days after vaccination, PB that secrete antibodies specific for the vaccine appear in the blood (Heilmann et al, 1987; Barington et al, 1990) and form a significant fraction of the total PB (Odendahl et al, 2005; Wrammert et al, 2008). It also exploited techniques that we had previously used to generate monoclonal antibodies from blood-borne PB by RT-PCR and cloning and expression of the DNA encoding the antigen-binding site from single PB (Babcook et al, 1996).…”

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

“…Because organisms like pneumococci are carried in the nasopharynx, it is not clear whether primary immunization of adults with the vaccine results in stimulation of naïve B cells or cells that had been previously primed through nasopharyngeal exposure to the organism. Other published data indicate that these responses are not limited to Pnc7 as the appearance of antigen specific, spontaneously secreting B cells in the peripheral blood, at days 5–8 after immunization, have been described after immunization with tetanus, influenza and pneumococcal vaccines 12,15–18 . The time from immunization to the production of these effector B cells indicates that, in the absence of a sustained protective antibody concentration, there is a window of several days in which invasive bacteria could cause disease even in a primed individual.…”