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BiIA-SG: When administered to SHIV-infected rhesus macaques, BiIA-SG prevented infection and slowed disease progression.
Niu2021
(immunotherapy)
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BiIA-SG: A single gene–encoded tandem bispecific immunoadhesin molecule BiIA-SG was developed, where 2 single-chain variable fragment (scFv) binding domains against the V3 glycan epitope recognized by the PGT128 mAb and the CD4 receptor recognized by Hu5A8 (iMab) are simultaneously present. This is a radically different approach compared with previous bispecifcs that included a single scFv for each bNAb. The neutralizing breadth and potency of the new BiIA-SG molecule were higher than those of the original neutralizing PGT128 mAb, or the BiIA-DG with a single scFv domain, possibly due to the ability of the anti-CD4 arm to bring the PGT128 arm in proximity to the HIV-1 Env, and also possibly due to the presence of 2 binding sites that favor the binding of the molecule to the targeted antigens. 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.
Wu2018
(antibody generation, immunoprophylaxis, bispecific/trispecific, broad neutralizer)
References
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2 references.
Isolation Paper
Wu2018
Xilin Wu, Jia Guo, Mengyue Niu, Minghui An, Li Liu, Hui Wang, Xia Jin, Qi Zhang, Ka Shing Lam, Tongjin Wu, Hua Wang, Qian Wang, Yanhua Du, Jingjing Li, Lin Cheng, Hang Ying Tang, Hong Shang, Linqi Zhang, Paul Zhou, and Zhiwei Chen. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. J Clin Invest, 128(6):2239-2251, Jun 1 2018. PubMed ID: 29461979.
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Niu2021
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, and Zhiwei Chen. Tandem bispecific antibody prevents pathogenic SHIVSF162P3CN infection and disease progression. Cell Rep, 36(8):109611 doi, Aug 2021. PubMed ID: 34433029
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