Shengxue Luo1,2,3, Panli Zhang2,3, Bochao Liu2,3, Chan Yang4, Chaolan Liang2,3, Qi Wang2,3, Ling Zhang2, Xi Tang2,5, Jinfeng Li2,6, Shuiping Hou2,7, Jinfeng Zeng8, Yongshui Fu2,9, Jean-Pierre Allain2,10, Tingting Li2, Yuming Zhang1, Chengyao Li2. 1. Department of Pediatrics, Shenzhen Hospital, Southern Medical University, Shenzhen, People's Republic of China. 2. Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, People's Republic of China. 3. Guangzhou Bai Rui Kang (BRK) Biological Science and Technology Limited Company, People's Republic of China. 4. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China. 5. Department of Infection, The First People's Hospital of Foshan, Foshan, People's Republic of China. 6. Shenzhen Key Laboratory of Molecular Epidemiology, Shenzhen Center for Disease Control and Prevention, Shenzhen, People's Republic of China. 7. Guangzhou Center for Disease Control and Prevention, Guangzhou, People's Republic of China. 8. Shenzhen Blood Center, Shenzhen, People's Republic of China. 9. Guangzhou Blood Center, Guangzhou, People's Republic of China. 10. Emeritus Professor, University of Cambridge, Cambridge, UK.
Abstract
ABSTRACTCOVID-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 × 109 PFU Sad23L-nCoV-S, followed by boosting with 5 × 109 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 103.16 anti-S, 102.75 anti-RBD binding antibody and 102.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 101.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/106 cells), IL-2 (334 SFCs/106 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.
ABSTRACTCOVID-19 vaccines are being developed urgently worldwide. Here, we constructed two n class="Species">adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2spike 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 × 109 PFU Sad23L-nCoV-S, followed by boosting with 5 × 109 PFUAd49L-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 103.16 anti-S, 102.75 anti-RBD binding antibody and 102.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 101.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/106 cells), IL-2 (334 SFCs/106 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.
Entities:
Keywords:
COVID-19 vaccines; human adenovirus 49 vector; mice and non-human primates; prime-boost vaccination; simian adenovirus 23 vector
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