A Potent Bispecific Nanobody Protects HACE2 Mice Against SARS-CoV-2 Infection Via Intranasal Administration

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Oct 13

PMID 34644535

Citations 48

Authors

Xilin Wu

Lin Cheng

Ming Fu

Bilian Huang

Linjing Zhu

Shijie Xu

Haixia Shi

Doudou Zhang

Huanyun Yuan

Waqas Nawaz

Ping Yang

Qinxue Hu

Yalan Liu

Zhiwei Wu

Affiliations

Soon will be listed here.

Abstract

The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb-Nb-Nb, a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb-Nb-Nb exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb-Nb-Nb provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb-Nb-Nb is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.

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