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.

• Authors: Boris Julg, Lawrence J Tartaglia, Brandon F Keele, Kshitij Wagh, Amarendra Pegu, Devin Sok, Peter Abbink, Stephen D Schmidt, Keyun Wang, Xuejun Chen, M G Joyce, Ivelin S Georgiev, Misook Choe, Peter D Kwong, Nicole A Doria-Rose, Khoa Le, Mark K Louder, Robert T Bailer, Penny L Moore, Bette Korber, Michael S Seaman, Salim S Abdool Karim, Lynn Morris, Richard A Koup, John R Mascola, Dennis R Burton, Dan H Barouch
• Journal: Science translational medicine (Sci Transl Med) Vol. 9 Issue 406 (09 06 2017) ISSN: 1946-6242 [Electronic] United States
• PMID: 28878010 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Antibodies, Neutralizing
• HIV Envelope Protein gp120

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Neutralizing (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Female
• HIV Envelope Protein gp120 (chemistry, metabolism)
• HIV-1 (metabolism)
• Macaca mulatta
• Male
• Neutralization Tests
• Sequence Alignment
• Simian Acquired Immunodeficiency Syndrome (blood, immunology, prevention & control, virology)
• Simian Immunodeficiency Virus (immunology)
• Viral Load