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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author 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
author_facet 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
author_sort Rachel Kim
collection DOAJ
description 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.
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spelling doaj-art-b3fc02ff9a1d41b089139d1b524104cd2025-08-20T03:20:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15710921571092A novel and safe SmartCap® SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humansRachel Kim0Tae-Gi Uhm1Jisu Kim2Dayeon Woo3Uk-Il Kim4Xue Meng5Byounggu Yang6Suhyeon Kim7Heejene Kim8Jonghyeon Kim9Sunkyung Yoon10Joo-Young Lee11Byungkyun Kim12Dongheon Cho13Duckho Chang14Young-Hwan Cho15Kanghyun Choi16WonSeok Gwak17Hoon-Woo Lee18Jieun Bang19Elizabeth Hellström20Byoungguk Kim21Kyungjin Kim22Joo-Sung Yang23R&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaDivision of Clinical Research for vaccine, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaDivision of Clinical Research for vaccine, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaBe Part Research (PTY) Ltd., Paarl, South AfricaDivision of Clinical Research for vaccine, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaR&D Center, ST Pharm Co., Ltd., Seoul, Republic of KoreaWe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1571092/fullmRNA vaccineCOVID-19SARS-CoV-2STP2104human clinical trial studyCapping Library Screening
spellingShingle 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
A novel and safe SmartCap® SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humans
Frontiers in Immunology
mRNA vaccine
COVID-19
SARS-CoV-2
STP2104
human clinical trial study
Capping Library Screening
title A novel and safe SmartCap® SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humans
title_full A novel and safe SmartCap® SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humans
title_fullStr A novel and safe SmartCap® SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humans
title_full_unstemmed A novel and safe SmartCap® SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humans
title_short A novel and safe SmartCap® SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humans
title_sort novel and safe smartcap r sc101 to develop the covid 19 mrna vaccine stp2104 inducing potent immune responses in humans
topic mRNA vaccine
COVID-19
SARS-CoV-2
STP2104
human clinical trial study
Capping Library Screening
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1571092/full
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