Discovery and development of a safe and efficient COVID-19 mRNA vaccine, STP2104, using a novel capping library screening method
Messenger RNA (mRNA) vaccines represent a critical avenue for coronavirus disease 2019 (COVID-19) prevention. We developed a COVID-19 mRNA vaccine encoding a codon-optimized full-length ancestral spike (S) protein with a signal peptide, which employs our novel patented co-transcriptional 5'-capping reagent, SmartCap<sup>®</sup>. From the screening capping library of SmartCap<sup>®</sup>, an SC101 cap was selected to derive a novel mRNA vaccine, STP2104. An <i>in vitro</i> study of STP2104 incorporating SC101 revealed enhanced protein expression in both the cell lysate and culture medium, and an <i>in vivo</i> immunogenicity study revealed strong humoral and cell-mediated immune responses. STP2104 further displayed potent neutralizing activity in immunized mice as derived via the PRNT<sub>50</sub> assay using the wild-type virus. We evaluated the protection efficacy of STP2104 using human ACE2 transgenic mice immunized and challenged with SARS-CoV-2 to acquire the survival rate, virus titration, and histopathology study data. These studies proved that STP2104 is potent enough to induce protective immunity. A novel capping library screening (CLS) method was successfully utilized for exploring the optimal 5'-cap reagent, which improves S gene expression with mRNA stability. The clinical phase 1 studies of STP2104 will prove its safety, tolerability, and immunogenicity as well as the safety of the novel 5'-cap analogue SC101 in humans.
Authors
- So‐Hee Hong (ORCID: https://orcid.org/0000-0002-2833-8025)
- Seeun Kim (ORCID: https://orcid.org/0000-0002-1949-451X)
- Yejin Yun (ORCID: https://orcid.org/0000-0002-0719-9599)
- Joo-Sung Yang
- H.-R. Kim
- S.H. Lee
- Tae Han Uhm
- Sohyun Park (ORCID: https://orcid.org/0000-0002-8192-7048)
- In-Young Lee (ORCID: https://orcid.org/0000-0003-1282-515X)
- Eui Geum Oh (ORCID: https://orcid.org/0000-0002-6941-0708)
- Uk-Il Kim
- Soochong Kim (ORCID: https://orcid.org/0000-0002-6739-9787)
- Eun‐Ji Kwon (ORCID: https://orcid.org/0000-0001-7057-3953)
- Hanah Lim
- Misu Kwon (ORCID: https://orcid.org/0000-0001-9324-0166)
- Gamin Kim (ORCID: https://orcid.org/0000-0001-8504-7921)
- Yoo‐Jin Bang
- Suhyun Park (ORCID: https://orcid.org/0009-0002-1926-8368)
- Young Oh Kweon (ORCID: https://orcid.org/0000-0001-5708-7985)
- Dokeun Kim
- Jaeyong Kim (ORCID: https://orcid.org/0000-0003-1787-3775)
- Eunjoo H. Lee (ORCID: https://orcid.org/0000-0002-5569-0067)
- Sang‐Myeong Lee (ORCID: https://orcid.org/0000-0002-3624-3392)
- Kyu Young Choi (ORCID: https://orcid.org/0000-0001-8464-2665)
- B. Kim
- Jung Ho Kim (ORCID: https://orcid.org/0000-0003-4931-3553)
- Kyung‐Jin Kim (ORCID: https://orcid.org/0000-0002-0375-2561)
- Sun-Hee Lee (ORCID: https://orcid.org/0009-0005-8145-4024)
- Seoyeon Kim (ORCID: https://orcid.org/0000-0003-2132-5245)
- Jong-Eun Lee (ORCID: https://orcid.org/0000-0002-1367-9249)
- Tae-Young Lee
- Ruijing Sun
- Sang-Hoon Song (ORCID: https://orcid.org/0000-0002-0812-5444)
- Jae-Hwan Nam
- You-Jin Kim
- Yun-Ho Hwang
- Joo-Young Lee
Institutions
- Sogang University (KR)
- Chungbuk National University (KR)
- Korea Pharma (South Korea) (KR)
- Korea Disease Control and Prevention Agency (KR)
- Korea Center for Disease Control and Prevention (KR)
- Catholic University of Korea (KR)
- Baewha Women's University (KR)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-06-09
- DOI
- https://doi.org/10.3389/fimmu.2025.1571713
- Citations
- 1
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Korea Disease Control and Prevention Agency
- Ministry of Trade, Industry and Energy
- Korea Health Industry Development Institute
- Korea Evaluation Institute of Industrial Technology