A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo

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.

Automated summary

Neutralizing antibodies are not as effective in therapeutic models as in prophylactic models due to limited efficacy in eliminating virus-producing cells. A SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy is presented, which blocks viral entry and eliminates infected cells through T cell-mediated cytotoxicity. S-BiTE is effective against both original and Delta variants of SARS-CoV-2, suggesting potential application against immune-escaping variants. In a humanized mouse model with live SARS-CoV-2 infection, S-BiTE significantly reduces viral load compared to neutralization treatment only.