PROJECT SUMMARY Despite advances in treatment in recent years, HIV is still responsible for more than half a million deaths annually; new infections have, furthermore, continued to exceed the milestones set by public health institutions. Recently, a number of candidate immunogens based on either germline targeting or epitope focusing have moved to Phase 1 clinical trials. These developments in HIV vaccinology have been immensely aided by improved technology for the generation of humanized mouse models, which can be used in iterative immunogen design, early stage down-selection, and other important components of vaccine development. Among those improvements include the multiplexed CRISPR/Cas9 dual immunoglobulin heavy and light chain knockins (KI) developed by the Batista lab. With this approach, mice with B cells bearing genuine human BCRs, which can be produced in a matter of weeks. Here, the Batista lab proposes to use this approach and its expertise in animal experiments to act as the Animal Model Core (AMC) for the Multi-Omics Vaccine Evaluation (MOVE) Consortium. The AMC will develop up to six new KI lines based on MOVE's interrogation of the naïve human B cell repertoire. The AMC will furthermore contribute its existing HIV models to immunization experiments initiated by MOVE Project 1. Samples generated from murine lymph, spleen, and other tissues will then be provided to MOVE Project 2 for immunocharacterization. The AMC will act as the fulcrum of prime and boost stage immunogen, formulation, and regiment development and assessment.