A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants
Chang Yi Wang, Kao-Pin Hwang, Hui-Kai Kuo, Wen-Jiun Peng, Yea-Huei Shen, Be-Sheng Kuo, Juin-Hua Huang, Hope Liu, Yu-Hsin Ho, Feng Lin, Shuang Ding, Zhi Liu, Huan-Ting Wu, Ching-Tai Huang, Yuarn-Jang Lee, Ming-Che Liu, Yi-Ching Yang, Po-Liang Lu, Hung-Chin Tsai, Chen-Hsiang Lee, Zhi-Yuan Shi, Chun-Eng Liu, Chun-Hsing Liao, Feng-Yee Chang, Hsiang-Cheng Chen, Fu-Der Wang, Kuo-Liang Hou, Jennifer Cheng, Min-Sheng Wang, Ya-Ting Yang, Han-Chen Chiu, Ming-Han Jiang, Hao-Yu Shih, Hsuan-Yu Shen, Po-Yen Chang, Yu-Rou Lan, Chi-Tian Chen, Yi-Ling Lin, Jian-Jong Liang, Chun-Che Liao, Yu-Chi Chou, Mary Kate Morris, Carl V Hanson, Farshad Guirakhoo, Michael Hellerstein, Hui-Jing Yu, Chwan-Chuen King, Tracy Kemp, D Gray Heppner, Thomas P Monath, Chang Yi Wang, Kao-Pin Hwang, Hui-Kai Kuo, Wen-Jiun Peng, Yea-Huei Shen, Be-Sheng Kuo, Juin-Hua Huang, Hope Liu, Yu-Hsin Ho, Feng Lin, Shuang Ding, Zhi Liu, Huan-Ting Wu, Ching-Tai Huang, Yuarn-Jang Lee, Ming-Che Liu, Yi-Ching Yang, Po-Liang Lu, Hung-Chin Tsai, Chen-Hsiang Lee, Zhi-Yuan Shi, Chun-Eng Liu, Chun-Hsing Liao, Feng-Yee Chang, Hsiang-Cheng Chen, Fu-Der Wang, Kuo-Liang Hou, Jennifer Cheng, Min-Sheng Wang, Ya-Ting Yang, Han-Chen Chiu, Ming-Han Jiang, Hao-Yu Shih, Hsuan-Yu Shen, Po-Yen Chang, Yu-Rou Lan, Chi-Tian Chen, Yi-Ling Lin, Jian-Jong Liang, Chun-Che Liao, Yu-Chi Chou, Mary Kate Morris, Carl V Hanson, Farshad Guirakhoo, Michael Hellerstein, Hui-Jing Yu, Chwan-Chuen King, Tracy Kemp, D Gray Heppner, Thomas P Monath
Abstract
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.
Keywords: COVID-19; Peptides.
Conflict of interest statement
Conflict of interest: CYW is cofounder and a board member of UBI, United BioPharma, and UBI Asia, and is named as an inventor on a patent application covering the composition of matter of this SARS-CoV-2 vaccine (Wang CY, et al., “Designer peptides and proteins for the detection, prevention and treatment of coronavirus disease, 2019 [COVID 19],” WO2021/168305A1. International publication date August 26, 2021. Priority data: 62/978,596 on February 19, 2020; 62/990,382 on March 16, 2020; 63/027,290 on May 19, 2020; and 63/118,596 on November 25, 2020). WJP, FL, and SD are named as coinventors on the same patent application covering this SARS-CoV-2 vaccine. CYW, HKK, WJP, BSK, HL, YHH, FL, SD, ZL, HTW, KLH, JC, MSW, YTY, JHH, HCC, MHJ, HYS, PYC, and YRL are employees within the UBI group. HJY, DGH, TK, FG, MH, and TPM are employees of Vaxxinity and hold share options in Vaxxinity. CYW is also a shareholder of Vaxxinity. DGH, TK, and TPM are also consultants to Public Health Vaccines LLC. TPM reports consulting fees from Merck and Memgen. TPM reports holding shares in Vaxess, Inc., which is engaged in development of a SARS-CoV-2 vaccine delivery device.
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Source: PubMed