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B-cell receptors (BCRs) specific for M72 are transmembrane proteins on the surface of B-lymphocytes that specifically recognize and bind the M72 recombinant fusion protein, a key component of the M72/AS01E tuberculosis vaccine candidate (Van Der Meeren et al., 2018, NEJM). The M72 antigen is a fusion of two Mycobacterium tuberculosis proteins, Mtb32A and Mtb39A, designed to elicit protective immune responses (Tait et al., 2019, NEJM). Upon binding of the M72 antigen to these BCRs, the B-cells are activated and undergo clonal expansion and differentiation into memory B-cells and plasma cells that secrete anti-M72 antibodies (Gillard et al., 2016, Vaccine). This humoral immune response, alongside T-cell activation, is intended to provide long-term protection against the progression of latent tuberculosis infection to active disease (Gates MRI, 2023). The presence and magnitude of M72-specific BCRs and antibodies are critical indicators of the vaccine's immunogenicity and are monitored as primary endpoints in clinical trials (WHO, 2022).
The M72 antigen within the M72/AS01E vaccine binds to and cross-links specific B-cell receptors, initiating a signaling cascade that results in B-cell activation, clonal expansion, and the production of high-affinity IgG antibodies against Mycobacterium tuberculosis (Van Der Meeren et al., 2018).
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