Recent insights from prophylactic passive immunization trials of HIV-1 broadly neutralizing antibodies: implications for vaccine design.

PURPOSE OF REVIEW: An HIV-1 vaccine remains an urgent need, underscored by funding cuts that threaten treatment programs. The antibody mediated prevention (AMP) trials confirmed that broadly neutralizing antibodies (bNAbs) can prevent HIV-1 acquisition, and provided paradigm-shifting insights into HIV-1 biology and protective thresholds. This review discusses the implications of these findings for HIV-1 vaccine design and identifies some of the key knowledge gaps that remain.

RECENT FINDINGS: The AMP trials emphasized the necessity of potent, broad bNAbs to prevent HIV-1 acquisition. Subsequent pharmacokinetic and neutralization analyses defined quantitative thresholds of protection, essential for benchmarking future success. However, questions remain regarding the extrapolation of VRC01-derived PT80 to other bNAbs and modes of transmission. Deep envelope sequencing from the AMP trials has revised our understanding of the transmission bottleneck, by revealing frequent multilineage infections and co-transmission of viruses with different sensitivities to VRC01. These factors challenge prevention and favour rapid escape under antibody pressure.

SUMMARY: These studies have provided essential immunological and virological insights relevant to HIV-1 vaccine design, and have refined our understanding of protective thresholds and early viral events. Together, these findings emphasize the need for combinations of potent, broad antibodies and better define the barriers to HIV-1 vaccine design.