Researchers have identified a relatively potent immunogen that could be harnessed to induce the immune system to target HIV. Recently, evidence suggests that using immunogens that prompt B cells to produce broadly neutralizing antibodies (bnAbs) may be a viable HIV vaccine strategy. In previous work, Joseph Jardine and colleagues demonstrated this possibility by using an immunogen that could bind to B cells engineered to express VRC01 class bnAbs (a class of highly broad and potent bnAbs) as well as their germline precursors. Yet questions remain as to whether immunogens can bind to naïve human B cells and whether enough naïve B cells are present in various individuals to make this strategy viable. Here, by analyzing a library of immunogens and comparing their potency, Jardine et al. identify an immunogen, eOD-GT8, which demonstrated extraordinary binding affinity for naïve B cells - it outperforms their previously identified immunogen by a factor of 2100. Next, they analyzed millions of B cells from 15 people who tested negative for HIV, to gain a better understanding of the prevalence of B cells that could interact with eOD-GT8. Their analysis indicates that about 96% of humans harbor such B cells, suggesting that eOD-GT8 is a promising candidate for future vaccines.