Article
作者: Liao, Chun-Che ; Lin, Yi-Ling ; Liang, Jian-Jong ; Morris, Mary Kate ; Yu, Hui-Jing ; Ding, Shuang ; Peng, Wen-Jiun ; Yang, Yi-Ching ; Shen, Yea-Huei ; Huang, Juin-Hua ; Wu, Huan-Ting ; Shen, Hsuan-Yu ; Chang, Po-Yen ; Hanson, Carl V ; Kuo, Be-Sheng ; Chou, Yu-Chi ; Monath, Thomas P ; Shi, Zhi-Yuan ; Lee, Yuarn-Jang ; King, Chwan-Chuen ; Hou, Kuo-Liang ; Yang, Ya-Ting ; Lin, Feng ; Guirakhoo, Farshad ; Heppner, D Gray ; Huang, Ching-Tai ; Kuo, Hui-Kai ; Hwang, Kao-Pin ; Tsai, Hung-Chin ; Chen, Hsiang-Cheng ; Liu, Zhi ; Liu, Hope ; Chen, Chi-Tian ; Cheng, Jennifer ; Lee, Chen-Hsiang ; Lan, Yu-Rou ; Chiu, Han-Chen ; Wang, Fu-Der ; Jiang, Ming-Han ; Liu, Ming-Che ; Shih, Hao-Yu ; Lu, Po-Liang ; Kemp, Tracy ; Wang, Chang Yi ; Ho, Yu-Hsin ; Liao, Chun-Hsing ; Liu, Chun-Eng ; Chang, Feng-Yee ; Wang, Min-Sheng ; Hellerstein, Michael
BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 μg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.