Abstract
Anthrax Vaccine Adsorbed (AVA) generates short-lived protective antigen (PA) specific IgG that correlates with in vitro toxin neutralization and protection from Bacillus anthracis challenge. Animal studies suggest that when PA-specific IgG has waned, survival after spore challenge correlates with an activation of PA-specific memory B cells. Here, we characterize the quantity and the longevity of AVA-induced memory B cell responses in humans. Peripheral blood mononuclear cells (PBMCs) from individuals vaccinated ≥3 times with AVA (n = 50) were collected early (3–6 months, n = 27) or late after their last vaccination (2–5 years, n = 23), pan-stimulated, and assayed by ELISPOT for total and PA-specific memory B cells differentiated into antibody secreting cells (ASCs). PA-specific ASC percentages ranged from 0.02% to 6.25% (median: 1.57%) and did not differ between early and late post-vaccination individuals. PA-specific ASC percentages correlated with plasma PA-specific IgG (r = 0.42, p = 0.03) and toxin neutralization (r = 0.52, p = 0.003) early post vaccination. PA-specific ASC percentages correlated with supernatant anti-PA both early (r = 0.60, p = 0.001) and late post vaccination (r = 0.71, p < 0.0001). These data suggest PA-specific memory B cell responses are long-lived and can be estimated after recent vaccination by the magnitude and neutralization capacity of the humoral response.
Highlights
The generation of immunological memory to T cell-dependent antigens results in both humoral and cellular immunity
We find that individuals sampled early and late post vaccination with similar levels of plasma anti-protective antigen (PA) IgG
PA-specific memory B cells is highly variable, and humoral measures may only serve as a surrogate measure in the first year after vaccination
Summary
The generation of immunological memory to T cell-dependent antigens results in both humoral and cellular immunity. In this process, naïve B cells enter the germinal center reaction and exit as antibody secreting cells (ASCs; plasmablasts or long-lived plasma cells) or memory B cells [1]. ASCs and memory B cells are responsible for maintaining humoral immunity generated by vaccination [2]. In mouse and Rhesus macaque studies in which antibody titers to PA are allowed to decline prior to challenge with anthrax spores, subsets of animals survive challenge and demonstrate evidence of memory B cell activation in the form of increased post-challenge PA antibody levels [11,14]. We hypothesized that antibody levels are maintained by long-lived plasma cells independent of memory B cells; while antibody and memory B cells may correlate early post-vaccination due to a relatively good or poor germinal center reaction, we expected the correlation of memory B cells and antibody levels to decline late post vaccination
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