@article{7e254e36a4c5458680dcea1478198367,
title = "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.",
author = "Wang, {Chang Yi} and Hwang, {Kao Pin} and Kuo, {Hui Kai} and Peng, {Wen Jiun} and Shen, {Yea Huei} and Kuo, {Be Sheng} and Huang, {Juin Hua} and Hope Liu and Ho, {Yu Hsin} and Feng Lin and Shuang Ding and Zhi Liu and Wu, {Huan Ting} and Huang, {Ching Tai} and Lee, {Yuarn Jang} and Liu, {Ming Che} and Yang, {Yi Ching} and Lu, {Po Liang} and Tsai, {Hung Chin} and Lee, {Chen Hsiang} and Shi, {Zhi Yuan} and Liu, {Chun Eng} and Liao, {Chun Hsing} and Chang, {Feng Yee} and Chen, {Hsiang Cheng} and Wang, {Fu Der} and Hou, {Kuo Liang} and Jennifer Cheng and Wang, {Min Sheng} and Yang, {Ya Ting} and Chiu, {Han Chen} and Jiang, {Ming Han} and Shih, {Hao Yu} and Shen, {Hsuan Yu} and Chang, {Po Yen} and Lan, {Yu Rou} and Chen, {Chi Tian} and Lin, {Yi Ling} and Liang, {Jian Jong} and Liao, {Chun Che} and Chou, {Yu Chi} and Morris, {Mary Kate} and Hanson, {Carl V.} and Farshad Guirakhoo and Michael Hellerstein and Yu, {Hui Jing} and King, {Chwan Chuen} and Tracy Kemp and Heppner, {D. Gray} and Monath, {Thomas P.}",
note = "Funding Information: The study was funded by UBI Asia (study sponsor), Vaxxinity Inc., and the Taiwan Centers for Disease Control, Ministry of Health and Welfare. The sponsor co-designed the trial and coordinated interactions with contract Clinical Research Organization (CRO) StatPlus staff and regulatory authorities. The CRO took charge of trial operation to meet the required standards of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and GCP guidelines. The IDMC oversaw the safety data and gave recommendations to the sponsor. The interim analysis was done by the CRO StatPlus. We thank all the trial participants for their dedication to these trials, the investigation staff at all trial hospital sites, and members of the IDMC for their dedication and guidance. Special thanks are also extended to the clinical associates from StatPlus, Inc and UBI Asia; the CMC task forces from both United BioPharma, Inc. and UBI Pharma, Inc; team members at the Institute of Biomedical Sciences, Academia Sinica for the live virus neutralization assay; and team members at the RNAi Core Facility, Academia Sinica for the pseudovi-rus neutralization assay. All HCS were supplied by the Biobank at the National Health Research Institutes (NHRI), Taiwan. Finally, special administrative support by Jalon Tai, Liang Kai Huang, Fran Volz, Chao-Hung Li, and Meng-Chung Lung from the UBI group is also acknowledged with gratitude. The findings and conclusions in this article are those of the authors and do not necessarily represent the views or opinions of the California Department of Public Health of the California Health and Human Services Agency. Publisher Copyright: {\textcopyright} 2022, Wang et al.",
year = "2022",
month = may,
day = "16",
doi = "10.1172/JCI157707",
language = "English",
volume = "132",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "10",
}
