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

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 neutra...

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Bibliographic Details
Published in:Science translational medicine 2017-09, Vol.9 (406)
Main Authors: Julg, Boris, Tartaglia, Lawrence J, Keele, Brandon F, Wagh, Kshitij, Pegu, Amarendra, Sok, Devin, Abbink, Peter, Schmidt, Stephen D, Wang, Keyun, Chen, Xuejun, Joyce, M G, Georgiev, Ivelin S, Choe, Misook, Kwong, Peter D, Doria-Rose, Nicole A, Le, Khoa, Louder, Mark K, Bailer, Robert T, Moore, Penny L, Korber, Bette, Seaman, Michael S, Abdool Karim, Salim S, Morris, Lynn, Koup, Richard A, Mascola, John R, Burton, Dennis R, Barouch, Dan H
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies, Neutralizing - immunology
CD4-Positive T-Lymphocytes - immunology
Female
HIV Envelope Protein gp120 - chemistry
HIV Envelope Protein gp120 - metabolism
HIV-1 - metabolism
Macaca mulatta
Male
Neutralization Tests
Sequence Alignment
Simian Acquired Immunodeficiency Syndrome - blood
Simian Acquired Immunodeficiency Syndrome - immunology
Simian Acquired Immunodeficiency Syndrome - prevention & control
Simian Acquired Immunodeficiency Syndrome - virology
Simian Immunodeficiency Virus - immunology
Viral Load
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Summary: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
ISSN:1946-6234
1946-6242
1946-6242
DOI:10.1126/scitranslmed.aal1321