The Journal of Clinical Investigation (May 2022)

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

Journal volume & issue
Vol. 132, no. 10

Abstract

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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.

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