A novel and safe SmartCap® SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humans

We have developed a 5′-capping library screening (CLS) method using over 30 different novel cap analogues. The optimal 5′-cap for the coronavirus disease 2019 (COVID-19) mRNA vaccine STP2104 was selected and applied. This is the first report to describe the proven safety of the novel cap analogue, S...

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Main Authors: Rachel Kim, Tae-Gi Uhm, Jisu Kim, Dayeon Woo, Uk-Il Kim, Xue Meng, Byounggu Yang, Suhyeon Kim, Heejene Kim, Jonghyeon Kim, Sunkyung Yoon, Joo-Young Lee, Byungkyun Kim, Dongheon Cho, Duckho Chang, Young-Hwan Cho, Kanghyun Choi, WonSeok Gwak, Hoon-Woo Lee, Jieun Bang, Elizabeth Hellström, Byoungguk Kim, Kyungjin Kim, Joo-Sung Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1571092/full
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Summary:We have developed a 5′-capping library screening (CLS) method using over 30 different novel cap analogues. The optimal 5′-cap for the coronavirus disease 2019 (COVID-19) mRNA vaccine STP2104 was selected and applied. This is the first report to describe the proven safety of the novel cap analogue, SmartCap® SC101, in humans and emphasize the importance of cap selection. STP2104 demonstrates safety, tolerability, and strong immune responses in humans. After confirming its safety through a GLP toxicity study, STP2104 was administered intramuscularly as a two-dose vaccine, separated by 28 days, in COVID-19-naive, healthy adult volunteers. In this multicenter, open-label, dose-escalation, phase I study with 30 participants (18 to 55 years of age), 15 individuals each were assigned to the low-dose (25 μg) and high-dose (50 μg) cohorts. The primary endpoints were the safety and immunogenicity in all cohorts. During the reporting period of the trial, no serious adverse events were reported. A plaque reduction neutralization test demonstrated an at least 21-fold increase in NAb titers from both cohorts when comparing pre-vaccination to 4-week post-second vaccination. These safety and NAb titer interim results support the efficiency and safety of SC101 and the STP2104 mRNA vaccine, including how STP2104 effectively induces NAb titers against SARS-CoV-2.
ISSN:1664-3224