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 9 PFU Sad23L-nCoV-S, followed by boosting with 5 × 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-γ (712.6 SFCs/10 6 cells), IL-2 (334 SFCs/10 6 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.
【저자키워드】 COVID-19 vaccines, simian adenovirus 23 vector, human adenovirus 49 vector, prime-boost vaccination, mice and non-human primates, 【초록키워드】 Vaccine, COVID-19 vaccine, immune response, immunogenicity, Immunity, T-cell Response, peptide, CD4, immunization, Spike protein, Adenovirus, T cell, cells, mice, animals, immune responses, response, SARS-CoV-2 spike protein, peptides, macaque, trials, IFN-γ, IL-2, rhesus macaques, macaques, rhesus macaque, anti-RBD, binding antibody, followed by, changes, preparation, dose-dependent manner, candidate, prime-boost regimen, nCoV, priming, anti-S, Specific, full-length, pseudovirus neutralizing antibody, FIVE, pathologic, detectable, evaluated, elicit, the vaccine, 【제목키워드】 COVID-19 vaccine, vaccination, Adenovirus, rhesus macaques, rhesus macaque, candidate,