Tandem bispecific antibody prevents pathogenic SHIVSF162P3CN infection and disease progression.

Abstract

Although progress has been made on constructing potent bi-specific broadly neutralizing antibody (bi-bNAb), few bi-bNAbs have been evaluated against HIV-1/AIDS in non-human primates (NHPs). Here, we report the efficacy of a tandem bi-bNAb, namely BiIA-SG, in Chinese-origin rhesus macaques (CRM) against the CRM-adapted R5-tropic pathogenic SHIVSF162P3CN challenge. Pre-exposure BiIA-SG injection prevents productive viral infection in 6 of 6 CRMs with unmeasurable proviral load, T cell responses, and seroconversion. Single BiIA-SG injection, at day 1 or 3 post viral challenge, significantly reduces peak viremia, achieves undetectable setpoint viremia in 8 of 13 CRMs, and delays disease progression for years in treated CRMs. In contrast, 6 of 8 untreated CRMs develop simian AIDS within 2 years. BiIA-SG-induced long-term protection is associated with CD8+ T cells as determined by anti-CD8β antibody depletion experiments. Our findings provide a proof-of-concept that bi-bNAb treatment elicits T cell immunity in NHPs, which warrant the clinical development of BiIA-SG for HIV-1 prevention and immunotherapy.

• Authors: Mengyue Niu, Yik Chun Wong, Hui Wang, Xin Li, Chun Yin Chan, Qi Zhang, Lijun Ling, Lin Cheng, Ruoke Wang, Yanhua Du, Lok Yan Yim, Xia Jin, Haoji Zhang, Linqi Zhang, Zhiwei Chen
• Journal: Cell reports (Cell Rep) Vol. 36 Issue 8 Pg. 109611 (08 24 2021) ISSN: 2211-1247 [Electronic] United States
• PMID: 34433029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Bispecific
• Antibodies, Neutralizing
• HIV Antibodies

Topics

• Animals
• Antibodies, Bispecific (pharmacology)
• Antibodies, Neutralizing (immunology)
• CD8-Positive T-Lymphocytes (immunology, virology)
• HIV Antibodies (immunology)
• HIV Infections (immunology, prevention & control)
• HIV-1 (drug effects, immunology)
• Macaca mulatta
• Simian Acquired Immunodeficiency Syndrome (immunology, virology)
• Simian Immunodeficiency Virus (immunology)