ASC frequency was reported as both the number of ASCs per 1×106 PBMC and the percentage of total IgG-secreting cells

ASC frequency was reported as both the number of ASCs per 1×106 PBMC and the percentage of total IgG-secreting cells. which represent important preclinical models for TB vaccine development. We observe a strong correlation between antibody titers in serum versus plasma with modestly higher titers in serum. We also report for the first time the rapid and transient Ginsenoside Rh2 induction of antibody-secreting plasmablasts following BCG vaccination, together with a robust and durable memory B cell response in humans. Finally, we demonstrate a functional role for BCG vaccine-induced specific antibodies in opsonizing mycobacteria and enhancing macrophage phagocytosis (is an intracellular pathogen and the necessity for a T cell response in conferring acquired immunity to TB has been demonstrated in numerous studies (2C6). This has led to limited attention on the humoral response to TB, although emerging evidence suggests that antibodies may play a more significant role in protection than previously appreciated (7C10). Antibodies could contribute to protection directly through increasing phagocytosis and phagolysosome formation or bacterial neutralization, and/or indirectly through enhancing T cell-mediated immunity (7). It has recently been shown that compared to antibodies from patients with active TB disease (ATB), antibodies from individuals with latent TB infection (LTBI) have unique Fc functional profiles, selective binding to FcRIII and distinct antibody glycosylation patterns, and also that they drive enhanced phagolysosomal maturation, inflammasome activation and macrophage killing of intracellular (9). Bacillus Calmette Gurin (BCG) is the only currently available vaccine against TB. BCG confers incomplete and variable protection against pulmonary TB in adolescents and adults, and a new more efficacious TB vaccine is needed (11, 12). However, it is uncertain which aspects of the immune response a candidate vaccine should aim to induce in order to confer protection that is superior to BCG. Due to the important role of BCG vaccination in protecting infants from severe forms Ginsenoside Rh2 of TB disease, and its potential nonspecific effects protecting from all-cause mortality, most TB vaccine candidates are designed as a heterologous boost to a BCG prime (13, 14). It is thus critical to understand the immune response to BCG vaccination and which aspects will be, or would ideally be, induced or boosted. Furthermore, because BCG vaccination is partially protective, and can confer superior protection when administered intravenously in macaques (15, 16) or against sustained infection when administered as a revaccination in non-LTBI South African adolescents (17), studying the immune response to BCG offers a valuable opportunity to explore immune mechanisms of protection and apply these to inform the design of more efficacious TB vaccine candidates. Robust Th1 responses to BCG vaccination have been described and are generally considered to be essential, but not sufficient, for protection (18C21). A role for trained innate immunity, unconventional T cells and humoral immunity in BCG-mediated protection has been proposed (22C24). Indeed, in a correlates of risk analysis, levels of Ag85A-specific IgG were associated with reduced risk of TB disease in BCG-vaccinated South African infants (25). We have comprehensively reviewed what is currently known about the humoral immune response to BCG vaccination and revaccination across species (26). Ginsenoside Rh2 In brief, the literature presents inconsistent evidence for the induction of specific antibody responses following BCG vaccination, and the relevance of these responses is unclear, with support both for (25, 27C30) and against (28, 31C33) a protective function. Interestingly, recent evidence suggests that BCG vaccination can modulate antibody glycosylation patterns with potential relevance for functionality (34), and IgM titers were among the strongest markers of reduced bacterial burden following challenge of BCG immunized macaques (35). Antibodies are produced by antibody-secreting B cells (ASCs). Upon activation by recognition of their cognate antigen during infection or vaccination, B cells undergo clonal expansion and Rabbit Polyclonal to Tyrosinase differentiate into plasmablasts and memory B cells (mBCs) (36). While plasmablasts and plasma cells secrete antibody, mBCs can survive quiescently for decades, poised to rapidly respond to antigen re-stimulation by differentiating into short- and long-lived ASCs that can prolong the duration of high Ginsenoside Rh2 serum antibody levels (37, 38). It is generally accepted that.