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

Luo, Shengxue; Zhang, Panli; Liu, Bochao; Yang, Chan; Liang, Chaolan; Wang, Qi; Zhang, Ling; Tang, Xi; Li, Jinfeng; Hou, Shuiping; Zeng, Jinfeng; Fu, Yongshui; Allain, Jean-Pierre; Li, Tingting; Zhang, Yuming; Li, Chengyao

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.