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Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection.
Front Immunol. 2021; 12:697074.FI

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.

Authors+Show Affiliations

NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.University of Chinese Academy of Sciences, Beijing, China. Chinese Academy of Sciences, Shanghai, China.National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China. 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.AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.University of Chinese Academy of Sciences, Beijing, China. Chinese Academy of Sciences, Shanghai, China.NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China. Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China. Teaching Center for Writing and Communication, Tsinghua University, Beijing, China.Walvax Biotechnology Co., Ltd., Kunming, China.Walvax Biotechnology Co., Ltd., Kunming, China.Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China. Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China. School of Life Sciences, Tsinghua University, Beijing, China. Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, China. Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China.NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.Walvax Biotechnology Co., Ltd., Kunming, China.State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China. 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.Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.NexVac Research Center, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34262569

Citation

Li, Mingxi, et al. "Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection." Frontiers in Immunology, vol. 12, 2021, p. 697074.
Li M, Guo J, Lu S, et al. Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection. Front Immunol. 2021;12:697074.
Li, M., Guo, J., Lu, S., Zhou, R., Shi, H., Shi, X., Cheng, L., Liang, Q., Liu, H., Wang, P., Wang, N., Wang, Y., Fu, L., Xing, M., Wang, R., Ju, B., Liu, L., Lau, S. Y., Jia, W., ... Zhang, L. (2021). Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection. Frontiers in Immunology, 12, 697074. https://doi.org/10.3389/fimmu.2021.697074
Li M, et al. Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection. Front Immunol. 2021;12:697074. PubMed PMID: 34262569.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection. AU - Li,Mingxi, AU - Guo,Jingao, AU - Lu,Shuaiyao, AU - Zhou,Runhong, AU - Shi,Hongyang, AU - Shi,Xuanling, AU - Cheng,Lin, AU - Liang,Qingtai, AU - Liu,Hongqi, AU - Wang,Pui, AU - Wang,Nan, AU - Wang,Yifeng, AU - Fu,Lili, AU - Xing,Man, AU - Wang,Ruoke, AU - Ju,Bin, AU - Liu,Li, AU - Lau,Siu-Ying, AU - Jia,Wenxu, AU - Tong,Xin, AU - Yuan,Lin, AU - Guo,Yong, AU - Qi,Hai, AU - Zhang,Qi, AU - Huang,Zhen, AU - Chen,Honglin, AU - Zhang,Zheng, AU - Chen,Zhiwei, AU - Peng,Xiaozhong, AU - Zhou,Dongming, AU - Zhang,Linqi, Y1 - 2021/06/28/ PY - 2021/04/21/received PY - 2021/06/07/accepted PY - 2021/7/15/entrez PY - 2021/7/16/pubmed PY - 2021/7/31/medline KW - SARS-CoV-2 vaccine KW - chimpanzee adenovirus vector KW - protective immunity KW - single-dose immunization KW - spike protein SP - 697074 EP - 697074 JF - Frontiers in immunology JO - Front Immunol VL - 12 N2 - 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. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/34262569/Single_Dose_Immunization_With_a_Chimpanzee_Adenovirus_Based_Vaccine_Induces_Sustained_and_Protective_Immunity_Against_SARS_CoV_2_Infection_ L2 - https://doi.org/10.3389/fimmu.2021.697074 DB - PRIME DP - Unbound Medicine ER -