Recombinant chimpanzee adenovirus vector vaccine expressing the spike protein provides effective and lasting protection against SARS-CoV-2 infection in mice

Mingqing Lu; Kunpeng Liu; Yun Peng; Zhe Ding; Yingwen Li; Alexander Tendu; Xue Hu; Ge Gao; Weiwei Guo; Hang Liu; Juhong Rao; Jiaxuan Zhao; Miaoyu Chen; Zhiming Yuan; Gary Wong; Chao Shan; Yanfeng Yao; Jiaming Lan

doi:10.1016/j.virs.2022.05.006

August 2022

Mingqing Lu, Kunpeng Liu, Yun Peng, Zhe Ding, Yingwen Li, Alexander Tendu, Xue Hu, Ge Gao, Weiwei Guo, Hang Liu, Juhong Rao, Jiaxuan Zhao, Miaoyu Chen, Zhiming Yuan, Gary Wong, Chao Shan, Yanfeng Yao and Jiaming Lan. Recombinant chimpanzee adenovirus vector vaccine expressing the spike protein provides effective and lasting protection against SARS-CoV-2 infection in mice[J]. Virologica Sinica, 2022, 37(4): 581-590. doi: 10.1016/j.virs.2022.05.006

Citation: Mingqing Lu, Kunpeng Liu, Yun Peng, Zhe Ding, Yingwen Li, Alexander Tendu, Xue Hu, Ge Gao, Weiwei Guo, Hang Liu, Juhong Rao, Jiaxuan Zhao, Miaoyu Chen, Zhiming Yuan, Gary Wong, Chao Shan, Yanfeng Yao, Jiaming Lan. Recombinant chimpanzee adenovirus vector vaccine expressing the spike protein provides effective and lasting protection against SARS-CoV-2 infection in mice .VIROLOGICA SINICA, 2022, 37(4) : 581-590. http://dx.doi.org/10.1016/j.virs.2022.05.006

表达新冠病毒S蛋白的重组黑猩猩腺病毒载体疫苗在小鼠体内诱导有效和持久的免疫保护

陆明青 ^a,b,c ,
刘鲲鹏 ^b,c ,
彭云 ^d ,
丁哲 ^a,c ,
李颖汶 ^a,c ,
Alexander Tendu ^a,c ,
胡雪 ^b ,
高歌 ^d ,
郭伟伟 ^b,c ,
刘航 ^d ,
饶具红 ^b,c ,
赵家玄 ^b,c ,
陈苗宇 ^d ,
袁志明 ^d ,
王颂基 ^a,, ,
单超 ^b,, ,
姚艳丰 ^d,, ,
蓝佳明 ^a,,

a, 中国科学院分子病毒与免疫重点实验室, 中国科学院上海巴斯德研究所;
b, 中国科学院武汉病毒研究所;
c, 中国科学院大学;
d, 中国科学院武汉病毒研究所生物安全与大数据中心

通讯作者： 王颂基, garyckwong@ips.ac.cn; 单超, shanchao@wh.iov.cn; 姚艳丰, yaoyf@wh.iov.cn; 蓝佳明, jmlan@ips.ac.cn
收稿日期： 2021-12-14
录用日期： 2022-05-26

摘要

SARS-CoV-2感染严重威胁人类健康和社会稳定发展。随着疫苗的广泛接种，新冠病毒导致的病死率显著下降。然而，新冠疫苗诱导免疫保护的持久性以及疫苗对新出现的各种变异株的有效性引发人们关注。基于此，我们构建了表达SARS-CoV-2全长刺突蛋白S的重组黑猩猩腺病毒载体疫苗（AdC68-S）。单针或两针接种C57BL/6J小鼠后，均在其体内检测到了快速、高水平的体液和细胞免疫应答反应。更为难得的是，疫苗在小鼠体内诱导的中和抗体在接种后至少6个月內没有显著下降，且对部分变异株有中和作用。AdC68-S疫苗单针或两针接种后，在短期（21天）和长期（6个月）均可抵抗SARS-CoV-2感染小鼠。表现为免疫小鼠肺组织病毒载量和滴度显著下降以及病理学检查显示的AdC68-S免疫小鼠肺组织轻度异常。综上，本研究在小鼠体内证明了AdC68-S疫苗的有效性和持久性，为进一步的临床实验奠定了基础。
- 新冠病毒
- , 疫苗
- , 黑猩猩腺病毒载体
- , 中和抗体
- , 长期保护

Recombinant chimpanzee adenovirus vector vaccine expressing the spike protein provides effective and lasting protection against SARS-CoV-2 infection in mice

Mingqing Lu ^a,b,c ,
Kunpeng Liu ^b,c ,
Yun Peng ^d ,
Zhe Ding ^a,c ,
Yingwen Li ^a,c ,
Alexander Tendu ^a,c ,
Xue Hu ^b ,
Ge Gao ^d ,
Weiwei Guo ^b,c ,
Hang Liu ^d ,
Juhong Rao ^b,c ,
Jiaxuan Zhao ^b,c ,
Miaoyu Chen ^d ,
Zhiming Yuan ^d ,
Gary Wong ^a,, ,
Chao Shan ^b,, ,
Yanfeng Yao ^d,, ,
Jiaming Lan ^a,,

a CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China;
b State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;
c University of Chinese Academy of Sciences, Beijing, 100049, China;
d Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China

Corresponding author: Gary Wong, garyckwong@ips.ac.cn Chao Shan, shanchao@wh.iov.cn Yanfeng Yao, yaoyf@wh.iov.cn Jiaming Lan, jmlan@ips.ac.cn
Received Date: 14 December 2021
Accepted Date: 26 May 2022

Abstract

SARS-CoV-2 infection is a global public health threat. Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic. As expected, deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination. However, there are concerns over the duration of vaccine-induced protection, as well as their effectiveness against emerging variants of concern. Here, we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2 (AdC68-S). Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of AdC68-S. Notably, neutralizing antibodies were observed up to at least six months after vaccination, without substantial decline. Single or double doses AdC68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term (21 days) and long-term (6 months). Histopathological examination of AdC68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection. Taken together, this study demonstrates the efficacy and durability of the AdC68-S vaccine and constitutes a promising candidate for clinical evaluation.
- SARS-CoV-2
- , Vaccine
- , Chimpanzee adenovirus vector
- , Neutralizing antibodies
- , Long-term protection

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