1. A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants
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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, and Monath, Thomas P.
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Immunological research ,Antigenic determinants -- Research ,Health care industry - Abstract
BACKGROUND. The 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. METHOD. We conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 [micro]g UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 [micro]g 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 [micro]g 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. RESULTS. No 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. CONCLUSION. UB-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 REGISTRATION. ClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742. FUNDING. UBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare., Introduction The combined effects of SARS-CoV-2 neutralization-escape variants with high transmissibility by asymptomatic persons (1, 2) and breakthrough infections due to waning immunity of COVID-19 vaccines (3-5) continue to cost [...]
- Published
- 2022
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