A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.
Клиническое исследование II фазыСтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wang Chang Yi, Hwang Kao-Pin, Kuo Hui-Kai, Peng Wen-Jiun, Shen Yea-Huei, Kuo Be-Sheng, Huang Juin-Hua, Liu Hope, Ho Yu-Hsin, Lin Feng, Ding Shuang, Liu Zhi, Wu Huan-Ting, Huang Ching-Tai, Lee Yuarn-Jang, Liu Ming-Che, Yang Yi-Ching, Lu Po-Liang, Tsai Hung-Chin, Lee Chen-Hsiang, Shi Zhi-Yuan, Liu Chun-Eng, Liao Chun-Hsing, Chang Feng-Yee, Chen Hsiang-Cheng, Wang Fu-Der, Hou Kuo-Liang, Cheng Jennifer, Wang Min-Sheng, Yang Ya-Ting, Chiu Han-Chen, Jiang Ming-Han, Shih Hao-Yu, Shen Hsuan-Yu, Chang Po-Yen, Lan Yu-Rou, Chen Chi-Tian, Lin Yi-Ling, Liang Jian-Jong, Liao Chun-Che, Chou Yu-Chi, Morris Mary Kate, Hanson Carl V, Guirakhoo Farshad, Hellerstein Michael, Yu Hui-Jing, King Chwan-Chuen, Kemp Tracy, Heppner D Gray, Monath Thomas P
Аннотация
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.