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 LeeZhi 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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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 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. 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.

Original languageEnglish
Article numbere157707
JournalJournal of Clinical Investigation
Volume132
Issue number10
DOIs
Publication statusPublished - May 16 2022

ASJC Scopus subject areas

  • Medicine(all)

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