Of Mice, Macaques, and Men: Broadly Neutralizing Antibody Immunotherapy for HIV-1

The neutralizing antibodies targeting the HIV-1 envelope protein have been a major focus for HIV therapy. Early studies with anti-HIV-1 neutralizing monoclonal antibodies (mAbs) administered to infected individuals showed some promise, as they resulted in transient reductions in plasma viremia in some recipients. However, resistant viral variants rapidly emerged. A major development during the past 6 to 7 years has been the isolation and characterization of highly potent and broadly neutralizing mAbs (bNAbs) from infected individuals known as "elite neutralizers." These "next-generation" bNAbs have been tested in animal model systems and shown to effectively control virus replication, particularly following combination immunotherapy. The success of these preclinical animal studies has led to human clinical trials using an individual bNAb for therapy. This review examines recent findings from animal models and human clinical trials and discusses the future use of bNAbs for HIV-1 treatment.