Imperial College London
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DrJiaGuo

Faculty of Medicine, Department of Infectious Disease

Research Associate
 
 
 
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Contact

 

jia.guo

 
 
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Location

 

Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wu:2018:10.1172/JCI96764,
author = {Wu, X and Guo, J and Niu, M and An, M and Liu, L and Wang, H and Jin, X and Zhang, Q and Lam, KS and Wu, T and Wang, H and Wang, Q and Du, Y and Li, J and Cheng, L and Tang, HY and Shang, H and Zhang, L and Zhou, P and Chen, Z},
doi = {10.1172/JCI96764},
journal = {Journal of Clinical Investigation},
pages = {2239--2251},
title = {Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice},
url = {http://dx.doi.org/10.1172/JCI96764},
volume = {128},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The discovery of an HIV-1 cure remains a medical challenge because the virus rebounds quickly after the cessation of combination antiretroviral therapy (cART). Here, we investigate the potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb) as an innovative product for HIV-1 prophylactic and therapeutic interventions. We discovered that by preserving 2 single-chain variable fragment (scFv) binding domains of each parental bnAb, a single gene–encoded tandem bs-bnAb, BiIA-SG, displayed substantially improved breadth and potency. BiIA-SG neutralized all 124 HIV-1–pseudotyped viruses tested, including global subtypes/recombinant forms, transmitted/founder viruses, variants not susceptible to parental bnAbs and to many other bnAbs with an average IC50 value of 0.073 μg/ml (range < 0.001–1.03 μg/ml). In humanized mice, an injection of BiIA-SG conferred sterile protection when administered prior to challenges with diverse live HIV-1 stains. Moreover, whereas BiIA-SG delayed viral rebound in a short-term therapeutic setting when combined with cART, a single injection of adeno-associated virus–transferred (AAV-transferred) BiIA-SG gene resulted dose-dependently in prolonged in vivo expression of BiIA-SG, which was associated with complete viremia control and subsequent elimination of infected cells in humanized mice. These results warrant the clinical development of BiIA-SG as a promising bs-bnAb–based biomedical intervention for the prevention and treatment of HIV-1 infection.
AU  - Wu,X
AU  - Guo,J
AU  - Niu,M
AU  - An,M
AU  - Liu,L
AU  - Wang,H
AU  - Jin,X
AU  - Zhang,Q
AU  - Lam,KS
AU  - Wu,T
AU  - Wang,H
AU  - Wang,Q
AU  - Du,Y
AU  - Li,J
AU  - Cheng,L
AU  - Tang,HY
AU  - Shang,H
AU  - Zhang,L
AU  - Zhou,P
AU  - Chen,Z
DO  - 10.1172/JCI96764
EP  - 2251
PY  - 2018///
SN  - 0021-9738
SP  - 2239
TI  - Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI96764
UR  - http://hdl.handle.net/10044/1/64307
VL  - 128
ER  -
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