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共表达狂犬病病毒糖蛋白(RABV G)和发热伴血小板减少综合征病毒糖蛋白(SFTSV Gn)的重组人5型腺病毒在小鼠中诱导针对狂犬病病毒和发热伴血小板减少综合征病毒的保护性免疫。

Recombinant Human Adenovirus Type 5 Co-expressing RABV G and SFTSV Gn Induces Protective Immunity Against Rabies Virus and Severe Fever With Thrombocytopenia Syndrome Virus in Mice.

作者信息

Zhao Zhongxin, Zheng Wenwen, Yan Lina, Sun Peilu, Xu Tong, Zhu Yelei, Liu Lele, Tian Li, He Hongbin, Wei Yurong, Zheng Xuexing

机构信息

Department of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.

Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, China.

出版信息

Front Microbiol. 2020 Jun 30;11:1473. doi: 10.3389/fmicb.2020.01473. eCollection 2020.

DOI:10.3389/fmicb.2020.01473
PMID:32695091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7339961/
Abstract

Both severe fever with thrombocytopenia syndrome (SFTS) and rabies are severe zoonotic diseases. As co-hosts of rabies virus (RABV) and SFTS virus (SFTSV), dogs and cats could not only be infected but also transmit the virus to human. Hence, developing a bivalent vaccine against both SFTS and rabies is urgently needed. In this study, we generated a recombinant replication-deficient human adenovirus type 5 (Ad5) co-expressing RABV G and SFTSV Gn (Ad5-G-Gn) and evaluated its immunogenicity and efficacy in mice. Ad5-G-Gn immunization activated more dendritic cells (DCs) and B cells in lymph nodes (LNs) and induced Th1-/Th2-mediated responses in splenocytes, leading to robust production of neutralizing antibodies against SFTSV and RABV. In addition, single dose of Ad5-G-Gn conferred mice complete protection against lethal RABV challenge and significantly reduced splenic SFTS viral load. Therefore, our data support further development of Ad5-G-Gn as a potential bivalent vaccine candidate against SFTS and rabies for dog and cat use.

摘要

严重发热伴血小板减少综合征(SFTS)和狂犬病均为严重的人畜共患病。犬猫作为狂犬病病毒(RABV)和SFTS病毒(SFTSV)的共同宿主,不仅会被感染,还能将病毒传播给人类。因此,迫切需要研发一种针对SFTS和狂犬病的二价疫苗。在本研究中,我们构建了一种共表达RABV G和SFTSV Gn的重组复制缺陷型人5型腺病毒(Ad5)(Ad5-G-Gn),并评估了其在小鼠体内的免疫原性和效力。Ad5-G-Gn免疫激活了淋巴结(LN)中更多的树突状细胞(DC)和B细胞,并在脾细胞中诱导了Th1/Th2介导的反应,从而导致针对SFTSV和RABV的中和抗体大量产生。此外,单剂量的Ad5-G-Gn使小鼠获得了针对致死性RABV攻击的完全保护,并显著降低了脾脏中的SFTS病毒载量。因此,我们的数据支持进一步将Ad5-G-Gn开发为一种潜在的用于犬猫的针对SFTS和狂犬病的二价疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/c0d6b7661fbf/fmicb-11-01473-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/7f4bd0ec0e58/fmicb-11-01473-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/25d0ce7c7ef2/fmicb-11-01473-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/39dc16cd75ba/fmicb-11-01473-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/7c0d4e4deb84/fmicb-11-01473-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/49bd9259471b/fmicb-11-01473-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/955dcfca9a83/fmicb-11-01473-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/c0d6b7661fbf/fmicb-11-01473-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/7f4bd0ec0e58/fmicb-11-01473-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/25d0ce7c7ef2/fmicb-11-01473-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/39dc16cd75ba/fmicb-11-01473-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/7c0d4e4deb84/fmicb-11-01473-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/49bd9259471b/fmicb-11-01473-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/955dcfca9a83/fmicb-11-01473-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f986/7339961/c0d6b7661fbf/fmicb-11-01473-g007.jpg

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