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Front Immunol
. 2025 Jun 9:16:1571713.
doi: 10.3389/fimmu.2025.1571713. eCollection 2025. Discovery and development of a safe and efficient COVID-19 mRNA vaccine, STP2104, using a novel capping library screening method
Kanghyun Choi # 1 , Joo-Young Lee # 1 , Uk-Il Kim # 1 , So-Hyun Park # 2 , So-Hee Hong # 3 , Yoo-Jin Bang # 4 , Yun-Ho Hwang # 5 , Jong-Eun Lee # 6 , Suhyun Park 1 , Soochong Kim 2 , Sunhee Lee 1 , Ye-Jin Yun 1 , Tae-Gi Uhm 1 , Inyoung Lee 1 , Minju Kwon 1 , EunJi Kwon 1 , Suyeon Song 1 , Yongkyoung Kweon 1 , Heejene Kim 1 , Eun-Young Oh 2 , Jae-Yong Kim 4 , Tae-Young Lee 5 , Seo-Yeon Kim 5 , Se-Eun Kim 5 , You-Jin Kim 5 , Seonock Lee 6 , Ruijing Sun 6 , Eun-Joo Lee 6 , Gamin Kim 6 , Hanah Lim 6 , Byungkyun Kim 1 , Jungho Kim 6 , Dokeun Kim 5 , Jae-Hwan Nam 4 , Sang-Myeong Lee 2 , Kyungjin Kim # 1 , Joo-Sung Yang # 1
Affiliations
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®. From the screening capping library of SmartCap®, an SC101 cap was selected to derive a novel mRNA vaccine, STP2104. An in vitro study of STP2104 incorporating SC101 revealed enhanced protein expression in both the cell lysate and culture medium, and an in vivo immunogenicity study revealed strong humoral and cell-mediated immune responses. STP2104 further displayed potent neutralizing activity in immunized mice as derived via the PRNT50 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.
Keywords: 5′-cap analogues; COVID-19; SARS-CoV-2; STP2104; SmartCap ®; capping library screening; mRNA vaccine.
. 2025 Jun 9:16:1571713.
doi: 10.3389/fimmu.2025.1571713. eCollection 2025. Discovery and development of a safe and efficient COVID-19 mRNA vaccine, STP2104, using a novel capping library screening method
Kanghyun Choi # 1 , Joo-Young Lee # 1 , Uk-Il Kim # 1 , So-Hyun Park # 2 , So-Hee Hong # 3 , Yoo-Jin Bang # 4 , Yun-Ho Hwang # 5 , Jong-Eun Lee # 6 , Suhyun Park 1 , Soochong Kim 2 , Sunhee Lee 1 , Ye-Jin Yun 1 , Tae-Gi Uhm 1 , Inyoung Lee 1 , Minju Kwon 1 , EunJi Kwon 1 , Suyeon Song 1 , Yongkyoung Kweon 1 , Heejene Kim 1 , Eun-Young Oh 2 , Jae-Yong Kim 4 , Tae-Young Lee 5 , Seo-Yeon Kim 5 , Se-Eun Kim 5 , You-Jin Kim 5 , Seonock Lee 6 , Ruijing Sun 6 , Eun-Joo Lee 6 , Gamin Kim 6 , Hanah Lim 6 , Byungkyun Kim 1 , Jungho Kim 6 , Dokeun Kim 5 , Jae-Hwan Nam 4 , Sang-Myeong Lee 2 , Kyungjin Kim # 1 , Joo-Sung Yang # 1
Affiliations
- PMID: 40552291
- PMCID: PMC12183165
- DOI: 10.3389/fimmu.2025.1571713
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®. From the screening capping library of SmartCap®, an SC101 cap was selected to derive a novel mRNA vaccine, STP2104. An in vitro study of STP2104 incorporating SC101 revealed enhanced protein expression in both the cell lysate and culture medium, and an in vivo immunogenicity study revealed strong humoral and cell-mediated immune responses. STP2104 further displayed potent neutralizing activity in immunized mice as derived via the PRNT50 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.
Keywords: 5′-cap analogues; COVID-19; SARS-CoV-2; STP2104; SmartCap ®; capping library screening; mRNA vaccine.