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一种稳定表达 SARS-CoV-2 受体结合域的流感病毒载体候选疫苗可在小鼠中产生高滴度和持久的中和抗体。

An influenza virus vector candidate vaccine stably expressing SARS-CoV-2 receptor-binding domain produces high and long-lasting neutralizing antibodies in mice.

机构信息

MOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

出版信息

Vet Microbiol. 2022 Aug;271:109491. doi: 10.1016/j.vetmic.2022.109491. Epub 2022 Jun 9.

DOI:10.1016/j.vetmic.2022.109491
PMID:35714529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9181763/
Abstract

Viral infectious pathogens, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, can cause extremely high infection rates and mortality in humans. Therefore, it is urgent to develop an effective vaccine against coronavirus and influenza virus infection. Herein, we used the influenza virus as a vector to express the SARS-CoV-2 spike receptor-binding domain (RBD) and hemagglutinin-esterase-fusion (HEF) protein of the influenza C virus. We then evaluated the feasibility and effectiveness of this design strategy through experiments in vitro and in vivo. The results showed that the chimeric viruses could stably express the HEF protein and the SARS-CoV-2 spike RBD at a high level. BALB/c mice, infected with the chimeric virus, exhibited mild clinical symptoms, yet produced high specific antibody levels against RBD and HEF, including neutralizing antibodies. Importantly, high neutralizing antibodies could be retained in the sera of mice for at least 20 weeks. Altogether, our data provided a new strategy for developing safe and effective COVID-19 and influenza virus vaccines.

摘要

病毒感染性病原体,如严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)和流感病毒,可在人类中引起极高的感染率和死亡率。因此,迫切需要开发针对冠状病毒和流感病毒感染的有效疫苗。在此,我们使用流感病毒作为载体来表达 SARS-CoV-2 的刺突受体结合域(RBD)和流感 C 病毒的血凝素-酯酶融合(HEF)蛋白。然后,我们通过体外和体内实验评估了这一设计策略的可行性和有效性。结果表明,嵌合病毒能够稳定地高水平表达 HEF 蛋白和 SARS-CoV-2 刺突 RBD。感染嵌合病毒的 BALB/c 小鼠表现出轻微的临床症状,但产生了针对 RBD 和 HEF 的高特异性抗体水平,包括中和抗体。重要的是,高中和抗体至少可在小鼠血清中保留 20 周。总之,我们的数据为开发安全有效的 COVID-19 和流感病毒疫苗提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/149e70dff365/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/edef39b52280/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/6941bef96432/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/6aface4445ac/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/5cbe6becb89e/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/600e0659727d/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/9ad6953ac2d5/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/242741cd7148/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/149e70dff365/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/edef39b52280/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/6941bef96432/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/6aface4445ac/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/5cbe6becb89e/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/600e0659727d/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/9ad6953ac2d5/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/242741cd7148/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6786/9181763/149e70dff365/gr8_lrg.jpg

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