病毒学：当前研究

Broadly Potent Neutralizing Bispecific Antibody against SARS-CoV-2

Abstract

Xianming Huang

The Omicron variant of Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) is threatening our global efforts fighting the COVID-19 pandemic. As the vast majority of current countermeasures against SARS-CoV-2 are completely or markedly losing their effectiveness, including most of the clinically approved neutralizing antibodies, better and more efficacious novel agents are urgently needed. We have developed a bispecific antibody, BAT2022, which bonds simultaneously with high affinity to two non-overlapping epitopes on the Receptor-Binding Domain (RBD), competitively blocks the binding of RBD to human Angiotensin-Converting Enzyme2 (ACE2) and potently neutralizes SARS-CoV-2 and all of the variants tested. The IC50 values in the pseudovirus assay for Omicron (BA.1) and Delta are 30 pM and 50 pM, respectively. A mouse model of SARS-CoV-2, BAT2022 showed strong prophylactic and therapeutic effects. Prophylactically, a single administration of BAT2022 completely protected mice from bodyweight loss, as compared with up to 20% loss of body weight in placebo- treated mice, reduced the lung viral titers to undetectable in all mice treated with BAT2022 either prophylactically or therapeutically, as compared with around 1 × 10⁵ pfu/g lung tissue in placebo-treated mice. Overall, Bispecific Antibody BAT2022 showed potent binding and neutralizing activity across a variety of SARS- CoV-2 variants and could be an attractive weapon to combat the ongoing waves of the Omicron pandemic.