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新型腺病毒载体 COVID-19 疫苗候选物对小鼠和食蟹猕猴的加强免疫接种。

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

机构信息

Department of Pediatrics, Shenzhen Hospital, Southern Medical University, Shenzhen, People's Republic of China.

Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, People's Republic of China.

出版信息

Emerg Microbes Infect. 2021 Dec;10(1):1002-1015. doi: 10.1080/22221751.2021.1931466.

Abstract

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 × 10 PFU Sad23L-nCoV-S, followed by boosting with 5 × 10 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 anti-S, 10 anti-RBD binding antibody and 10 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 10 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/10 cells), IL-2 (334 SFCs/10 cells) and intracellular IFN-γ 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.

摘要

新型冠状病毒肺炎(COVID-19)疫苗正在全球范围内紧急研发。在这里,我们构建了两种携带全长 SARS-CoV-2 刺突蛋白基因的腺病毒载体 COVID-19 疫苗候选物 Sad23L-nCoV-S 和 Ad49L-nCoV-S。单独在小鼠中评估了两种疫苗的免疫原性。通过剂量依赖性方式进行初免,观察到了特异性免疫反应,并且通过加强免疫获得了更强的反应。此外,用 5×10 PFU 的 Sad23L-nCoV-S 对五只恒河猴进行初免,然后在 4 周的间隔时间内用 5×10 PFU 的 Ad49L-nCoV-S 进行加强免疫。两种疫苗在小鼠和恒河猴中接种后均耐受良好,没有可检测到的临床或病理变化。在恒河猴中,初免-加强方案诱导了高滴度的 10 抗-S、10 抗-RBD 结合抗体和 10 假病毒中和抗体(pNAb),在初免后 2 个月达到峰值,而 pNAb 在初免后 7 个月逐渐下降至 10。在接种疫苗的恒河猴中检测到针对 S 肽的 IFN-γ(712.6 SFCs/10 细胞)、IL-2(334 SFCs/10 细胞)和 CD4/CD8 T 细胞内 IFN-γ(0.39%/0.55%)的强烈 T 细胞反应。结论是,Sad23L-nCoV-S 和 Ad49L-nCoV-S 的初免-加强免疫可以安全地在动物中引发强烈的免疫反应,为临床 I/II 期试验做准备。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6563/8172228/ac7aaeb63067/TEMI_A_1931466_F0001_OC.jpg

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