Tandem bispecific antibody prevents pathogenic SHIV SF162P3CN infection and disease progression.

Autor:	Niu M; AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China., Wong YC; AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China., Wang H; HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China., Li X; AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China; Department of Veterinary Medicine, Foshan University, Foshan, People's Repubic of China., Chan CY; AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China., Zhang Q; Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People's Republic of China., Ling L; AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China., Cheng L; HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China., Wang R; Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People's Republic of China., Du Y; AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China., Yim LY; AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China., Jin X; Translational Medical Research Institute, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China., Zhang H; Department of Veterinary Medicine, Foshan University, Foshan, People's Repubic of China., Zhang L; Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People's Republic of China., Chen Z; AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China; HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China. Electronic address: zchenai@hku.hk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Aug 24; Vol. 36 (8), pp. 109611.
DOI:	10.1016/j.celrep.2021.109611
Abstrakt:	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 SHIV SF162P3CN 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. Competing Interests: Declaration of interests Z.C. and H.W. are co-inventors of BiIA-SG. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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