Research ArticleHIV

Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge

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Science Translational Medicine  06 Sep 2017:
Vol. 9, Issue 406, eaal1321
DOI: 10.1126/scitranslmed.aal1321

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Potently protective antibodies

HIV is thought to be an elusive virus, but there are multiple epitopes on HIV that can be targeted by neutralizing antibodies, such as the V2 loop of the envelope protein. Julg et al. reasoned that potent anti-V2 HIV antibodies given prophylactically could prevent infection from taking place. They tested this in nonhuman primates with a novel clade C SHIV strain and observed protection at very low concentrations of circulating neutralizing antibody, suggesting that passive immunization with these types of antibodies might be protective in people.

Abstract

Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth against HIV-1. However, little data exist on the protective efficacy of V2-specific neutralizing antibodies. We created a novel SHIV-325c viral stock that included a clade C HIV-1 envelope and was susceptible to neutralization by both of these antibodies. Rhesus macaques received a single infusion of either antibody at three different concentrations (2, 0.4, and 0.08 mg/kg) before challenge with SHIV-325c. PGDM1400 was fully protective at the 0.4 mg/kg dose, whereas CAP256-VRC26.25-LS was fully protective even at the 0.08 mg/kg dose, which correlated with its greater in vitro neutralization potency against the challenge virus. Serum antibody concentrations required for protection were <0.75 μg/ml for CAP256-VRC26.25-LS. These data demonstrate unprecedented potency and protective efficacy of V2-specific neutralizing antibodies in nonhuman primates and validate V2 as a potential target for the prevention of HIV-1 infection in passive immunization strategies in humans.

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