Frontiers in Immunology (Jun 2021)
Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection
- Mingxi Li,
- Jingao Guo,
- Jingao Guo,
- Shuaiyao Lu,
- Shuaiyao Lu,
- Runhong Zhou,
- Runhong Zhou,
- Hongyang Shi,
- Hongyang Shi,
- Xuanling Shi,
- Lin Cheng,
- Lin Cheng,
- Qingtai Liang,
- Hongqi Liu,
- Pui Wang,
- Nan Wang,
- Yifeng Wang,
- Yifeng Wang,
- Yifeng Wang,
- Lili Fu,
- Man Xing,
- Ruoke Wang,
- Bin Ju,
- Bin Ju,
- Li Liu,
- Li Liu,
- Siu-Ying Lau,
- Wenxu Jia,
- Wenxu Jia,
- Xin Tong,
- Lin Yuan,
- Yong Guo,
- Hai Qi,
- Hai Qi,
- Hai Qi,
- Hai Qi,
- Hai Qi,
- Hai Qi,
- Qi Zhang,
- Zhen Huang,
- Honglin Chen,
- Zheng Zhang,
- Zheng Zhang,
- Zhiwei Chen,
- Zhiwei Chen,
- Xiaozhong Peng,
- Xiaozhong Peng,
- Dongming Zhou,
- Dongming Zhou,
- Linqi Zhang
Affiliations
- Mingxi Li
- NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China
- Jingao Guo
- University of Chinese Academy of Sciences, Beijing, China
- Jingao Guo
- Chinese Academy of Sciences, Shanghai, China
- Shuaiyao Lu
- National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Shuaiyao Lu
- State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
- Runhong Zhou
- AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Runhong Zhou
- State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Hongyang Shi
- University of Chinese Academy of Sciences, Beijing, China
- Hongyang Shi
- Chinese Academy of Sciences, Shanghai, China
- Xuanling Shi
- NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China
- Lin Cheng
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, China
- Lin Cheng
- The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China
- Qingtai Liang
- NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China
- Hongqi Liu
- National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Pui Wang
- State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Nan Wang
- 0Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
- Yifeng Wang
- 1Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
- Yifeng Wang
- 2Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China
- Yifeng Wang
- 3Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
- Lili Fu
- NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China
- Man Xing
- 4Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
- Ruoke Wang
- NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China
- Bin Ju
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, China
- Bin Ju
- The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China
- Li Liu
- AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Li Liu
- State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Siu-Ying Lau
- State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Wenxu Jia
- NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China
- Wenxu Jia
- 5Teaching Center for Writing and Communication, Tsinghua University, Beijing, China
- Xin Tong
- 6Walvax Biotechnology Co., Ltd., Kunming, China
- Lin Yuan
- 6Walvax Biotechnology Co., Ltd., Kunming, China
- Yong Guo
- 0Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
- Hai Qi
- 1Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
- Hai Qi
- 2Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China
- Hai Qi
- 3Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
- Hai Qi
- 7School of Life Sciences, Tsinghua University, Beijing, China
- Hai Qi
- 8Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, China
- Hai Qi
- 9Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China
- Qi Zhang
- NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China
- Zhen Huang
- 6Walvax Biotechnology Co., Ltd., Kunming, China
- Honglin Chen
- State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Zheng Zhang
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, China
- Zheng Zhang
- The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China
- Zhiwei Chen
- AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Zhiwei Chen
- State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Xiaozhong Peng
- National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
- Xiaozhong Peng
- State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
- Dongming Zhou
- 4Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
- Dongming Zhou
- 0Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Linqi Zhang
- NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China
- DOI
- https://doi.org/10.3389/fimmu.2021.697074
- Journal volume & issue
-
Vol. 12
Abstract
The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.
Keywords
- SARS-CoV-2 vaccine
- chimpanzee adenovirus vector
- spike protein
- single-dose immunization
- protective immunity
