The immune correlates of risk analysis and recent non-human primate (NHP) challenge studies have generated hypotheses that suggest HIV-1 envelope may be essential and, perhaps, sufficient to induce protective antibody responses against HIV-1 acquisition at the mucosal entry. New prime-boost mosaic and conserved-sequence, together with replicating vector immunisation strategies aiming at inducing immune responses or greater breadth, as well as the development of immunogens inducing broadly neutralising antibodies and mucosal responses, should be actively pursued and tested in humans. Whether the immune correlates of risk identified in RV144 can be extended to other vaccines, other populations, or different modes and intensity of transmission, and against increasing HIV-1 genetic diversity, remains to be demonstrated. Although NHP challenge studies may guide vaccine development, human efficacy trials remain key for answering the critical questions leading to the development of a global HIV-1 vaccine for licensure.
Keywords: HIV prevention; HIV vaccine; clinical trials; efficacy; immune correlates.