Can We Improve Vaccine Efficacy by Targeting T and B Cell Repertoire Convergence?

Traditional vaccine development builds on the assumption that healthy individuals have virtually unlimited antigen recognition repertoires of receptors in B cells and T cells [the B cell receptor (BCR) and TCR respectively]. However, there are indications that there are "holes" in the breadth of repertoire diversity, where no or few B or T cell are able to bind to a given antigen. Repertoire diversity may in these cases be a limiting factor for vaccine efficacy. Assuming that it is possible to predict which B and T cell receptors will respond to a given immunogen, vaccine strategies could be optimized and personalized. In addition, vaccine testing could be simplified if we could predict responses through sequencing BCR and TCRs. Bulk sequencing has shown putatively specific converging sequences after infection or vaccination. However, only single cell technologies have made it possible to capture the sequence of both heavy and light chains of a BCR or the alpha and beta chains the TCR. This has enabled the cloning of receptors and the functional validation of a predicted specificity. This review summarizes recent evidence of converging sequences in infectious diseases. Current and potential future applications of single cell technology in immune repertoire analysis are then discussed. Finally, possible short- and long-term implications for vaccine research are highlighted.