Multiple broadly neutralizing antibody lineages can co-exist and mature in the same germinal centres

An efficacious HIV vaccine will need to generate broadly neutralizing antibodies (bnAbs) against distinct viral epitopes. To facilitate this, immunogens targeting precursor B cells of bnAbs have been developed. With this strategy, individual immunogens can even target multiple lineages, thereby beneficially limiting the number of immunogens needed for a multi-bnAb generating vaccine. However, it is unclear whether this diminishes responses compared to isolated targeting of lineages with distinct immunogens. Here, we address this using an in silico model of naive B cell activation and affinity maturation in germinal centres. By incorporating (i) precursor properties and (ii) epitope masking by antibodies obtained from germinal centre-derived plasma cells, the model recapitulated features of bnAb lineage evolution as seen in pre-clinical mouse models. Subsequent model analysis suggested that under physiologically relevant conditions, priming of multiple bnAb lineages with a single immunogen was additive, thus, supporting the development of vaccines that target multiple lineages.