Neutralizing antibodies for HIV-1 prevention.

Abstract

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. 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. 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.