Induction of HIV broadly neutralizing antibodies with vaccination in humans in discovery medicine trials.

PURPOSE OF REVIEW: Since our last review of progress in inducing HIV broadly neutralizing antibodies (bnAbs) in 2023, advances have been made in achieving bnAb induction in humans. The purpose of this review is to discuss this progress and to outline remaining tasks needed to complete a prototype HIV vaccine.

RECENT FINDINGS: Several published clinical trials have succeeded in inducing bnAb precursors of multiple types, including membrane proximal external region (MPER), CD4+-mimicking CD4+-binding site (bs) and HCDR3-dominant CD4bs. Trials are underway or nearing completion for inducing V2-apex and V3-glycan bnAb precursors.

SUMMARY: Progress is being made in developing vaccine immunogens that induce bnAb B cell lineages in humans. The next tasks are to design boosting immunogens that complete bnAb affinity maturation, and to do so for two to three different bnAb specificities to prevent transmitted-founder virus escape during HIV transmission. A final task is to utilize a vaccine platform that will induce high-tittered, durable serum bnAb activity capable of providing protection for multiple years.