Neutralizing antibodies for HIV-1 prevention.

PURPOSE OF REVIEW: In the absence of a protective vaccine against HIV-1, passive immunization using novel broadly neutralizing antibodies (bNAbs) is an attractive concept for HIV-1 prevention. Here, we summarize the results of preclinical and clinical studies of bNAbs, discuss strategies for optimizing bNAb efficacy and lay out current pathways for the development of bNAbs as prophylaxis.

RECENT FINDINGS: Passive transfer of second-generation bNAbs results inpotent protection against infection in preclinical animal models. Furthermore, multiple bNAbs targeting different epitopes on the HIV-1 envelope trimer are in clinical evaluation and have demonstrated favorable safety profiles and robust antiviral activity in chronically infected individuals. The confirmation that passive immunization with bNAb(s) will prevent HIV-1 acquisition in humans is pending and the focus of ongoing investigations. Given the global diversity of HIV-1, bNAb combinations or multispecific antibodies will most likely be required to produce the necessary breadth for effective protection.

SUMMARY: Encouraging results from preclinical and clinical studies support the development of bNAbs for prevention and a number of antibodies with exceptional breadth and potency are available for clinical evaluation. Further optimization of viral coverage and antibody half-life will accelerate the clinical implementation of bNAbs as a critical tool for HIV-1 prevention strategies.