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强效双特异性纳米抗体经鼻内给药可保护 hACE2 小鼠免受 SARS-CoV-2 感染。

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

机构信息

Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China; Department of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, People's Republic of China.

Institute for Hepatology, National Clinical Research Center for Infectious, Disease, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China.

出版信息

Cell Rep. 2021 Oct 19;37(3):109869. doi: 10.1016/j.celrep.2021.109869. Epub 2021 Oct 6.

DOI:10.1016/j.celrep.2021.109869
PMID:34644535
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8492916/
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.

摘要

新冠肺炎（COVID-19）疫情迅速蔓延，需要采取多种有效对策。中和纳米抗体（Nbs）是治疗 COVID-19 的一种潜在治疗策略。在这里，我们从用严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突糖蛋白（S）免疫的羊驼的纳米抗体文库中鉴定了几种针对受体结合域（RBD）的 Nbs，其中三种 Nbs对 SARS-CoV-2 活病毒、假型病毒和循环 SARS-CoV-2 变体具有皮摩尔效力。为了提高它们的疗效，对各种 Nbs 进行了工程改造。Nb-Nb-Nb 是由三个 Nbs 构成的三聚体，被构建为对人血清白蛋白（HSA）和 SARS-CoV-2 的 RBD 具有双特异性。Nb-Nb-Nb 对野生型和 Delta 变体的 SARS-CoV-2 的中和效力为纳克/毫升级，在体内具有长半衰期。此外，我们表明，鼻内给予 Nb-Nb-Nb 可针对 hACE2 转基因小鼠的 SARS-CoV-2 感染提供针对预防和治疗的有效保护。Nb-Nb-Nb 是通过呼吸道给药预防和治疗 SARS-CoV-2 的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/50e0187fbe47/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/970184bfeaaf/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/77094f1cb366/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/1fd1535b360b/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/e84ed94c1824/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/bf35abba19a9/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/96f57c46f675/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/50e0187fbe47/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/970184bfeaaf/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/77094f1cb366/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/1fd1535b360b/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/e84ed94c1824/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/bf35abba19a9/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/96f57c46f675/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2431/8492916/50e0187fbe47/gr6_lrg.jpg

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