Broadly neutralizing antibodies are promising for HIV-1 prevention and therapy.

Newly identified bNAbs reveal novel epitopes and binding modes.

Effective restriction of HIV-1 escape can be achieved by bNAb combinations and a novel antibody.

First shock-and-kill approaches insufficient in reducing HIV-1 reservoir.

Proof-of-concept for bNAb-mediated HIV-1 prevention against sensitive virus.

Potent broadly neutralizing antibodies (bNAbs) targeting HIV-1 exhibit significant antiviral activity in humans. Recent advances have demonstrated that novel antibodies and bNAb combinations can effectively restrict the development of viral escape mutations. Moreover, passive immunization trials have provided proof-of-principle for bNAb-mediated prevention of infection with antibody-sensitive HIV-1 strains. In contrast, clinical studies investigating the activity of HIV-1 bNAbs on the latent reservoir failed to demonstrate substantial effects. Clinical adoption of HIV-1 bNAbs will require the development of more potent and broadly active antibodies as well as their implementation in optimized strategies to fully harness the capabilities of bNAbs. We review preclinical and clinical studies on HIV-1 bNAbs to highlight their potential and remaining limitations.

© 2022 Elsevier B.V. All rights reserved.