A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo.
A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo.
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DOI：
10.1038/s42003-023-04955-3
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发表时间：
2023-06-01
影响因子：
5.9
通讯作者：
Yang, Xuanming
中科院分区：
文献类型：
--
作者：
Li, Fanlin;Xu, Wei;Zhang, Xiaoqing;Wang, Wanting;Su, Shan;Han, Ping;Wang, Haiyong;Xu, Yanqin;Li, Min;Fan, Lilv;Zhang, Huihui;Dai, Qiang;Lin, Hao;Qi, Xinyue;Liang, Jie;Wang, Xin;Jiang, Shibo;Xie, Youhua;Lu, Lu;Yang, Xuanming
中和抗体对病毒进入有强有力的抑制作用；然而，它们在治疗模型中的效果不如在预防模型中的效果，可能是因为它们通过fc介导的细胞毒性消除产生病毒的细胞的功效有限。在此，我们提出了一种用于控制SARS-CoV-2感染的SARS-CoV-2刺突靶向双特异性t细胞接合器（S-BiTE）策略。这种方法通过与膜受体竞争来阻止游离病毒进入受纳细胞，并通过强大的T细胞介导的细胞毒性消除病毒感染的细胞。S-BiTE对SARS-CoV2的原始变体和δ变体均有效，效果相似，提示其对免疫逃逸变体的潜在应用。此外，在SARS-COV-2活感染人源化小鼠模型中，S-BiTE处理小鼠的病毒载量明显低于仅中和处理组。S-BiTE策略可能在对抗其他冠状病毒感染方面有广泛的应用。提出了一种SARS-CoV-2刺突靶向双特异性t细胞接触器（S-BiTE）策略，可有效降低人源化小鼠模型中SARS-CoV-2病毒载量。
Neutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with live SARS-COV-2 infection, S-BiTE treated mice showed significantly less viral load than neutralization only treated group. The S-BiTE strategy may have broad applications in combating other coronavirus infections. A SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy is presented that effectively reduces SARS-CoV-2 viral load in a humanized mouse model.
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