Prime-boost vaccination of mice and rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

被引:17
|
作者
Luo, Shengxue [1 ,2 ,3 ]
Zhang, Panli [2 ,3 ]
Liu, Bochao [2 ,3 ]
Yang, Chan [4 ]
Liang, Chaolan [2 ,3 ]
Wang, Qi [2 ,3 ]
Zhang, Ling [2 ]
Tang, Xi [2 ,5 ]
Li, Jinfeng [2 ,6 ]
Hou, Shuiping [2 ,7 ]
Zeng, Jinfeng [8 ]
Fu, Yongshui [2 ,9 ]
Allain, Jean-Pierre [2 ,10 ]
Li, Tingting [2 ]
Zhang, Yuming [1 ]
Li, Chengyao [2 ]
机构
[1] Southern Med Univ, Shenzhen Hosp, Dept Pediat, Shenzhen, Peoples R China
[2] Southern Med Univ, Sch Lab Med & Biotechnol, Dept Transfus Med, Guangzhou, Peoples R China
[3] Guangzhou Bai Rui Kang BRK Biol Sci & Technol, Guangzhou, Peoples R China
[4] Southern Med Univ, Sch Pharmaceut Sci, Guangzhou, Peoples R China
[5] First Peoples Hosp Foshan, Dept Infect, Foshan, Peoples R China
[6] Shenzhen Ctr Dis Control & Prevent, Shenzhen Key Lab Mol Epidemiol, Shenzhen, Guangdong, Peoples R China
[7] Guangzhou Ctr Dis Control & Prevent, Guangzhou, Peoples R China
[8] Shenzhen Blood Ctr, Shenzhen, Peoples R China
[9] Guangzhou Blood Ctr, Guangzhou, Peoples R China
[10] Univ Cambridge, Cambridge, England
关键词
COVID-19; vaccines; simian adenovirus 23 vector; human adenovirus 49 vector; prime-boost vaccination; mice and non-human primates; IMMUNOGENICITY; RESPONSES;
D O I
10.1080/22221751.2021.1931466
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
COVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5 x 10(9) PFU Sad23L-nCoV-S, followed by boosting with 5 x 10(9) PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 10(3.16) anti-S, 10(2.75) anti-RBD binding antibody and 10(2.38) pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 10(1.45) at 7 months post-priming. Robust T-cell response of IFN-gamma (712.6 SFCs/10(6) cells), IL-2 (334 SFCs/10(6) cells) and intracellular IFN-gamma in CD4+/CD8+ T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.
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页码:1002 / 1015
页数:14
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