A major obstacle to a broadly neutralizing antibody (bnAb)-based HIV vaccine is the activation of appropriate B cell precursors. Germline-targeting immunogens must be capable of priming rare bnAb precursors in the physiological setting. We tested the ability of the VRC01-class bnAb germline-targeting immunogen eOD-GT8 60mer to activate appropriate precursors in mice transgenic for human immunoglobulin loci. Despite an average frequency of at most ~1 VRC01-class precursor per mouse, we found that at least 29% of singly-immunized mice produced a VRC01-class memory response, suggesting that priming generally succeeded when at least one precursor was present. The results demonstrate the feasibility of using germline targeting to prime specific and exceedingly rare bnAb precursor B cells within a human-like repertoire.
Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice.