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

TitleBroadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge.
Publication TypeJournal Article
Year of Publication2017
AuthorsJulg 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, Karim SSAbdool, Morris L, Koup RA, Mascola JR, Burton DR, Barouch DH
JournalSci Transl Med
Volume9
Issue406
Date Published09/06/2017
ISSN1946-6242
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.

DOI10.1126/scitranslmed.aal1321
Alternate JournalSci Transl Med
PubMed ID28878010
PubMed Central IDPMC5755978
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
UM1 AI126603 / AI / NIAID NIH HHS / United States
U19 AI096040 / AI / NIAID NIH HHS / United States
UM1 AI124377 / AI / NIAID NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
K08 AI106408 / AI / NIAID NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
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