Figure 1.

Key figure. Prospective utility of antigen-specific MBC subphenotyping as a possible vaccine durability biomarker strategy.

MBC induction is thought to be a crucial component of vaccine durability. We propose that correlating particular distributions of circulating antigen-specific MBCs with existing vaccination strategies of known high- or low-efficacy/durability can inform the optimal distribution of MBC subphenotypes for novel vaccine candidates. For instance, if during testing, vaccine candidate B (right) induces a broad distribution of MBC subsets (as measured by single-cell analyses such as RNA sequencing or mass cytometry), particularly including established naïve-distal ‘advanced’ clusters (e.g., potentially CD19^hiCD11c⁺, CD95⁺) and/or recent germinal center (GC) emigrants, and this distribution is known to be elicited by successful vaccines of a similar immunogenic profile, then such distributions may be useful in predicting long-term candidate efficacy. However, if another candidate (A; left) elicits a more restricted or skewed MBC distribution (e.g., perhaps constituting more naïve-proximal, ‘early’, CD73^–CD95^– phenotypes), this might be an useful indicator of inefficient immune engagement or skewed immunogenic profile, therein providing early insights into deficits in long-term efficacy and indicating the potential need to modify the vaccination strategy in terms of the nature/dose of adjuvant, administration route, or even vaccine technology. Ultimately, whether particular MBC subphenotypes or distributions possess positive or negative predictive value remains to be experimentally substantiated. Created with BioRender.com. Abbreviations: Ag, antigen; MBC, memory B cell; UMAP, uniform manifold approximation and projection [36].