A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants
Chang Yi Wang, … , D. Gray Heppner, Thomas P. Monath
Chang Yi Wang, … , D. Gray Heppner, Thomas P. Monath
Published March 22, 2022
Citation Information: J Clin Invest. 2022;132(10):e157707. https://doi.org/10.1172/JCI157707.
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Clinical Research and Public Health

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants

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.Trial Registration ClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.Funding UBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Authors

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

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Figure 9

UB-612–induced long-lasting, robust Th1-predominant cell response measured by IFN-γ and IL-4 ELISpot after restimulation of PBMCs with designer peptide antigens.

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UB-612–induced long-lasting, robust Th1-predominant cell response measur...
In the 196-day phase I trial with 2 UB-612 doses on days 0 and 28, vaccine-induced T cell responses were measured by IFN-γ ELISpot with PBMCs from young adults (20–55 years old) in (A) 10, (B) 30, or (C) 100 μg dose group (n = 20 each). In the phase II trial study, participants (younger adults, 18–65 years old) received 2 doses of UB-612 at 100 μg (n = 88) or saline placebo (n = 12), and T cell responses in PBMCs of vaccinees on day 57 restimulated with designer antigen protein/peptides were measured by (D) IFN-γ and (E) IL-4 ELISpot. Shown are spot-forming units (SFU) per 1 × 106 PBMCs producing IFN-γ and IL-4 after stimulation with S1-RBD plus Th/CTL peptide pool, Th/CTL peptide pool, or SARS-CoV-2 T peptides (Th/CTL peptide pool without UBITh1a). Statistical analysis was performed with the use of the 2-sample t test. ****P < 0.0001.