tetano
Editor, Senior Moderator
Cell Rep
. 2021 Oct 6;109869.
doi: 10.1016/j.celrep.2021.109869. Online ahead of print.
A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration
Xilin Wu[SUP] 1 [/SUP], Lin Cheng[SUP] 2 [/SUP], Ming Fu[SUP] 3 [/SUP], Bilian Huang[SUP] 4 [/SUP], Linjing Zhu[SUP] 5 [/SUP], Shijie Xu[SUP] 1 [/SUP], Haixia Shi[SUP] 6 [/SUP], Doudou Zhang[SUP] 5 [/SUP], Huanyun Yuan[SUP] 5 [/SUP], Waqas Nawaz[SUP] 4 [/SUP], Ping Yang[SUP] 7 [/SUP], Qinxue Hu[SUP] 8 [/SUP], Yalan Liu[SUP] 9 [/SUP], Zhiwei Wu[SUP] 10 [/SUP]
Affiliations
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[SUB]15[/SUB]-Nb[SUB]H[/SUB]-Nb[SUB]15[/SUB], a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb[SUB]15[/SUB]-Nb[SUB]H[/SUB]-Nb[SUB]15[/SUB] 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[SUB]15[/SUB]-Nb[SUB]H[/SUB]-Nb[SUB]15[/SUB] provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb[SUB]15[/SUB]-Nb[SUB]H[/SUB]-Nb[SUB]15[/SUB] is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.
Keywords: Delta; Nb15; Nb15-NbH-Nb15; SARS-CoV-2; VHH; bispecific; hACE2 mice; intranasal; nanobody; potent neutralizing.
. 2021 Oct 6;109869.
doi: 10.1016/j.celrep.2021.109869. Online ahead of print.
A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration
Xilin Wu[SUP] 1 [/SUP], Lin Cheng[SUP] 2 [/SUP], Ming Fu[SUP] 3 [/SUP], Bilian Huang[SUP] 4 [/SUP], Linjing Zhu[SUP] 5 [/SUP], Shijie Xu[SUP] 1 [/SUP], Haixia Shi[SUP] 6 [/SUP], Doudou Zhang[SUP] 5 [/SUP], Huanyun Yuan[SUP] 5 [/SUP], Waqas Nawaz[SUP] 4 [/SUP], Ping Yang[SUP] 7 [/SUP], Qinxue Hu[SUP] 8 [/SUP], Yalan Liu[SUP] 9 [/SUP], Zhiwei Wu[SUP] 10 [/SUP]
Affiliations
- PMID: 34644535
- DOI: 10.1016/j.celrep.2021.109869
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[SUB]15[/SUB]-Nb[SUB]H[/SUB]-Nb[SUB]15[/SUB], a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb[SUB]15[/SUB]-Nb[SUB]H[/SUB]-Nb[SUB]15[/SUB] 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[SUB]15[/SUB]-Nb[SUB]H[/SUB]-Nb[SUB]15[/SUB] provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb[SUB]15[/SUB]-Nb[SUB]H[/SUB]-Nb[SUB]15[/SUB] is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.
Keywords: Delta; Nb15; Nb15-NbH-Nb15; SARS-CoV-2; VHH; bispecific; hACE2 mice; intranasal; nanobody; potent neutralizing.