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 5

In the phase II trial, virus-neutralizing titer (VNT50) against live SARS-CoV-2 WT after the primary 2-dose vaccination and the booster third dose.

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In the phase II trial, virus-neutralizing titer (VNT50) against live SAR...
In the primary 2-dose vaccination series of the 196-day phase I UB-612 trial, 60 participants were enrolled for the 10 μg, 30 μg, and 100 μg dose groups (n = 20 per group), of which 50 participants were enrolled for the extension study and received a booster third dose at 100 μg (n = 17 for the 10 μg; n = 15 for the 30 μg, and n = 18 for the 100 μg dose group). The virus-neutralizing antibody geometric mean titers (GMT, 95% CI) that inhibit 50% of live SARS-CoV-2 WT were measured and expressed as VNT50 for the (A) 10 μg, (B) 30 μg, and (C) 100 μg dose groups. (D) Illustrated with the 100 μg dose group, the VNT50 data were recorded on day 0 (before dose 1), day 14 (14 days after dose 1), day 28 (1 month after dose 1, before dose 2), day 42 (14 days after dose 2), day 56 (1 month after dose 2), day 112 (3 months after dose 2), day 196 (6 months after dose 2), days 255 to 316 before dose 3, the pre-booster, average day 286), and days 269 to 330 (14 days after booster, average day 300) for study participants of the 3 dose groups. The international unit (IU/mL) corresponding to 50% neutralizing GMT and 95% CI (VNT50) is shown in Supplemental Figure 3. The titers for individual participants are shown by the circles. The horizontal dotted lines indicate the lower limit of quantification. HCS, human convalescent serum samples in the control group (n = 20).