Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. We hypothesize that consistent bnAb elicitation will require ‘germline-targeting’ priming immunogens, to activate bnAb precursor B cells, and structure-guided, or ‘reductionist’, boosting immunogens, to shepherd antibody maturation toward bnAb development. To test this hypothesis, we have focused our initial immunogen design work on VRC01- and PGT121-class bnAbs, but we are addressing other bnAb classes as well, because an effective vaccine will likely need to induce multiple bnAbs of complementary specificities. Our efforts to design, evaluate and optimize the immunogens and immunization regimens are iterative, collaborative and multi-disciplinary. Overall, the work in progress represents an attempt to introduce a new way to design vaccines.