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

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.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Julg B,Tartaglia LJ,Keele BF,Wagh K,Pegu A,Sok D,Abbink P,Schmidt SD,Wang K,Chen X,Joyce MG,Georgiev IS,Choe M,Kwong PD,Doria-Rose NA,Le K,Louder MK,Bailer RT,Moore PL,Korber B,Seaman MS,Abdool Karim SS,Morris

doi

10.1126/scitranslmed.aal1321

subject

Has Abstract

pub_date

2017-09-06 00:00:00

issue

406

eissn

1946-6234

issn

1946-6242

pii

9/406/eaal1321

journal_volume

9

pub_type

杂志文章

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