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

Published version
Peer-reviewed

Type

Article

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Authors

Luo, Shengxue 
Zhang, Panli 
Liu, Bochao 
Yang, Chan 
Liang, Chaolan 

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.

Description

Keywords

COVID-19 vaccines, human adenovirus 49 vector, mice and non-human primates, prime-boost vaccination, simian adenovirus 23 vector, Adenoviridae, Animals, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, COVID-19 Vaccines, Female, Genetic Vectors, HEK293 Cells, Humans, Immunization, Secondary, Macaca mulatta, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, SARS-CoV-2, T-Lymphocytes

Journal Title

Emerg Microbes Infect

Conference Name

Journal ISSN

2222-1751
2222-1751

Volume Title

10

Publisher

Informa UK Limited