B cell lineages that are the current focus of vaccine development efforts against HIV-1, influenza or coronaviruses, often contain rare features, such as long heavy chain complementarity determining regions (CDRH3) loops. These unusual characteristics may limit the number of available B cells in the natural immunoglobulin repertoire that can respond to pathogen vaccinations. To measure the ability of a given immunogen to engage naturally occurring B cell receptors of interest, here we describe a mixed experimental and bioinformatic approach for determining the frequency and sequence of CDRH3 loops in the immune repertoire that can be recognized by a vaccine candidate. By combining deep mutational scanning and B cell receptor database analysis, CDRH3 loops were found that can be engaged by two HIV-1 germline-targeting immunogens, thus illustrating how the methods described here can be used to evaluate candidate immunogens based on their ability to engage diverse B cell lineage precursors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.