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Review
. 2017 Aug 9;22(2):207-216.
doi: 10.1016/j.chom.2017.07.010.

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

Yoshiaki Nishimura  1 , Malcolm A Martin  2
Affiliations
Review

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

Yoshiaki Nishimura et al. Cell Host Microbe. .

Abstract

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.

Keywords: HIV 1 immunotherapy; HIV-1; HIV-1 neutralizing antibodies; SHIV; SHIV macaque model; bNAbs; hu-mice; monoclonal antibody therapy.

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Figures

Fig. 1
Fig. 1
bNAb Suppression of SHIV replication during acute infection. cART potently blocks multiple steps during virus replication. bNAbs bind to virions and inhibit particle entry. In addition, the infused bNAbs are able to form immune complexes with progeny virions that are continuously being produced. Antigen-presenting dendritic cells, expressing activating Fc receptors, can bind these immune complexes, resulting in dendritic cell activation and efficient antigen processing for presentation to CD4+ and CD8+ T cells.
Fig. 2
Fig. 2
Diagrammatic representations of virus control following cART and bNAb treatments. The effects of bNAb monotherapy (B) and cART treatment (C) of chronically HIV-1 infected humans and combination bNAb (D) and cART treatment (E)of acutely SHIVAD8 infected rhesus monkeys are shown.
See this image and copyright information in PMC

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