A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration

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 deri...

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Autores principales: Wu, Xilin, Cheng, Lin, Fu, Ming, Huang, Bilian, Zhu, Linjing, Xu, Shijie, Shi, Haixia, Zhang, Doudou, Yuan, Huanyun, Nawaz, Waqas, Yang, Ping, Hu, Qinxue, Liu, Yalan, Wu, Zhiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492916/
https://www.ncbi.nlm.nih.gov/pubmed/34644535
http://dx.doi.org/10.1016/j.celrep.2021.109869
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author Wu, Xilin
Cheng, Lin
Fu, Ming
Huang, Bilian
Zhu, Linjing
Xu, Shijie
Shi, Haixia
Zhang, Doudou
Yuan, Huanyun
Nawaz, Waqas
Yang, Ping
Hu, Qinxue
Liu, Yalan
Wu, Zhiwei
author_facet Wu, Xilin
Cheng, Lin
Fu, Ming
Huang, Bilian
Zhu, Linjing
Xu, Shijie
Shi, Haixia
Zhang, Doudou
Yuan, Huanyun
Nawaz, Waqas
Yang, Ping
Hu, Qinxue
Liu, Yalan
Wu, Zhiwei
author_sort Wu, Xilin
collection PubMed
description 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(15)-Nb(H)-Nb(15), a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb(15)-Nb(H)-Nb(15) 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(15)-Nb(H)-Nb(15) provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb(15)-Nb(H)-Nb(15) is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.
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spelling pubmed-84929162021-10-06 A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration Wu, Xilin Cheng, Lin Fu, Ming Huang, Bilian Zhu, Linjing Xu, Shijie Shi, Haixia Zhang, Doudou Yuan, Huanyun Nawaz, Waqas Yang, Ping Hu, Qinxue Liu, Yalan Wu, Zhiwei Cell Rep Article 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(15)-Nb(H)-Nb(15), a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb(15)-Nb(H)-Nb(15) 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(15)-Nb(H)-Nb(15) provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb(15)-Nb(H)-Nb(15) is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration. The Author(s). 2021-10-19 2021-10-06 /pmc/articles/PMC8492916/ /pubmed/34644535 http://dx.doi.org/10.1016/j.celrep.2021.109869 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Wu, Xilin
Cheng, Lin
Fu, Ming
Huang, Bilian
Zhu, Linjing
Xu, Shijie
Shi, Haixia
Zhang, Doudou
Yuan, Huanyun
Nawaz, Waqas
Yang, Ping
Hu, Qinxue
Liu, Yalan
Wu, Zhiwei
A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration
title A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration
title_full A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration
title_fullStr A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration
title_full_unstemmed A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration
title_short A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration
title_sort potent bispecific nanobody protects hace2 mice against sars-cov-2 infection via intranasal administration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492916/
https://www.ncbi.nlm.nih.gov/pubmed/34644535
http://dx.doi.org/10.1016/j.celrep.2021.109869
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