Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection

Li, Mingxi1; Guo, Jingao2,3; Lu, Shuaiyao4,5,6; Zhou, Runhong7,8; Shi, Hongyang2,3; Shi, Xuanling1; Cheng, Lin9,10; Liang, Qingtai1; Liu, Hongqi4,5; Wang, Pui8; Wang, Nan11; Wang, Yifeng12,13,14; Fu, Lili1; Xing, Man15; Wang, Ruoke1; Ju, Bin9,10; Liu, Li7,8; Lau, Siu-Ying8; Jia, Wenxu1,16; Tong, Xin17; Yuan, Lin17; Guo, Yong11; Qi, Hai12,13,14,18,19,20; Zhang, Qi1; Huang, Zhen17; Chen, Honglin8; Zhang, Zheng9,10; Chen, Zhiwei7,8; Peng, Xiaozhong4,5,6; Zhou, Dongming15,21; Zhang, Linqi1

2021-06-28

10.3389/fimmu.2021.697074

Frontiers in Immunology   影响因子和分区

1664-3224

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.

SARS-CoV-2 vaccine chimpanzee adenovirus vector spike protein single-dose immunization protective immunity

SCI

英语

其他

National Key Plan for Scientific Research and Development of China["2020YFC0848800","2020YFC0844200","2018ZX10731101-002","2017ZX10201101","2016YFD0500307"] ; National Natural Science Foundation of China[31870922,32070926,81530065,91442127] ; Science and Technology Innovation Committee of Shenzhen Municipality[202002073000002] ; Tsinghua University Initiative Scientific Research Program[20201080053] ; Beijing Municipal Science and Technology Commission[171100000517,"Z201100005420019"] ; Tsinghua University Spring Breeze Fund[2020Z99CFG004]

Immunology

Immunology

WOS:000671836100001

FRONTIERS MEDIA SA

Web of Science

1.Tsinghua Univ, NexVac Res Ctr, Comprehens AIDS Res Ctr, Beijing Adv Innovat Ctr Struct Biol,Sch Med, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Shanghai, Peoples R China
4.Chinese Acad Med Sci, Inst Med Biol, Natl Kunming High Level Biosafety Primate Res Ctr, Kunming, Yunnan, Peoples R China
5.Peking Union Med Coll, Kunming, Yunnan, Peoples R China
6.Chinese Acad Med Sci, Sch Basic Med,Peking Union Med Coll, Inst Basic Med Sci,Med Primate Res Ctr,Neurosci C, State Key Lab Med Mol Biol,Dept Mol Biol & Bioche, Beijing, Peoples R China
7.Univ Hong Kong, Li Ka Shing Fac Med, AIDS Inst, Hong Kong, Peoples R China
8.Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, State Key Lab Emerging Infect Dis, Hong Kong, Peoples R China
9.Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Inst Hepatol, Shenzhen, Peoples R China
10.Southern Univ Sci & Technol, Affiliated Hosp 2, Sch Med, Shenzhen, Peoples R China
11.Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing, Peoples R China
12.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing, Peoples R China
13.Tsinghua Univ, Inst Immunol, Lab Dynam Immunobiol, Beijing, Peoples R China
14.Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing, Peoples R China
15.Tianjin Med Univ, Sch Basic Med Sci, Dept Pathogen Biol, Tianjin, Peoples R China
16.Tsinghua Univ, Teaching Ctr Writing & Commun, Beijing, Peoples R China
17.Walvax Biotechnol Co Ltd, Kunming, Yunnan, Peoples R China
18.Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China
19.Tsinghua Univ, Beijing Key Lab Immunol Res Chron Dis, Beijing, Peoples R China
20.Tsinghua Univ, Beijing Frontier Res Ctr Biol Struct, Beijing, Peoples R China
21.Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai, Peoples R China

Li, Mingxi,Guo, Jingao,Lu, Shuaiyao,et al. Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection[J]. Frontiers in Immunology,2021,12.

Li, Mingxi.,Guo, Jingao.,Lu, Shuaiyao.,Zhou, Runhong.,Shi, Hongyang.,...&Zhang, Linqi.(2021).Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection.Frontiers in Immunology,12.

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 12(2021).