Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection causes acquired immune deficiency syndrome (AIDS), a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART) but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs) with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

Keywords: HIV-1; antibody therapy; broadly neutralizing antibody; epitope.

Figure 1

The human immunodeficiency virus type 1 (HIV-1) broadly neutralizing antibodies (bNAbs) epitopes on envelope glycoprotein spike (Env) trimer. The surface representation of Env is derived from the crystal structure of BG505 SOSIP.664 (PDB no. 4TVP). Major HIV-1 Env epitopes are highlighted in different colors (CD4bs (red), V1/V2 (tv-blue), V3/Asn332 glycan patch (green), gp120/gp41-interface (wheat), MPER (denoted as gray rectangle)) and their representative bNAbs are listed in the right boxes. Other unspecified regions are in light grey for gp120 moiety and in dark grey for the gp41 moiety. The structural figure was generated with the program PyMOL (http://www.pymol.org/).