Broadly neutralizing antibodies suppress HIV in the persistent viral reservoir

Abstract

Several highly potent and broadly neutralizing monoclonal antibodies against HIV have recently been isolated from B cells of infected individuals. However, the effects of these antibodies on the persistent viral reservoirs in HIV-infected individuals receiving antiretroviral therapy (ART) are unknown. We show that several HIV-specific monoclonal antibodies--in particular, PGT121, VRC01, and VRC03--potently inhibited entry into CD4(+) T cells of HIV isolated from the latent viral reservoir of infected individuals whose plasma viremia was well controlled by ART. In addition, we demonstrate that HIV replication in autologous CD4(+) T cells derived from infected individuals receiving ART was profoundly suppressed by three aforementioned and other HIV-specific monoclonal antibodies. These findings have implications for passive immunotherapy as an approach toward controlling plasma viral rebound in patients whose ART is withdrawn.

Keywords: HIV envelope protein; HIV-specific antibodies; latent HIV.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Effect of broadly reactive HIV-specific monoclonal antibodies on virus isolated from latently infected resting CD4+ T cells obtained from HIV-infected individuals receiving ART. (A) Representative data showing fold increase of virions bound to a panel of broadly reactive HIV-specific monoclonal antibodies over negative control (human IgG). (B) Cumulative data showing fold increase of virions bound to a panel of broadly reactive HIV-specific monoclonal antibodies over negative control (human IgG). The fold increases of the binding of virions to HIV-neutralizing antibodies over the control antibody (human IgG) were compared by using the studentized range test. The geometric mean values are shown as black bars.

Fig. 2.

Effect of broadly reactive HIV-specific monoclonal antibodies on virus isolated from latently infected resting CD4+ T cells obtained from HIV-infected individuals receiving ART. (A) Representative data showing log suppression of viral entry into CD4+ T cells obtained from HIV-uninfected donors by HIV-specific monoclonal antibodies over negative control (human IgG). (B) Cumulative data showing log suppression of viral entry into CD4+ T cells obtained from HIV-uninfected donors by HIV-specific antibodies over negative control (human IgG). The log suppression of viral entry over the control antibody (human IgG) was compared by using the studentized range test. The mean values are shown as black bars.

Fig. 3.

Effect of broadly reactive HIV-specific monoclonal antibodies on viral replication in autologous CD4+ T cells of infected individuals whose viremia was controlled on ART. CD4+ T cells from nine study subjects were stimulated with anti-CD3/CD28 antibodies in the presence of two HIV-specific monoclonal antibodies (20 µg/mL; individually or in combination) that exhibited the highest levels of inhibition of HIV entry. The cultures were maintained for 9 d and the level of viral replication was determined by HIV p24 ELISA.