A viral codon usage strategy enhances antigen production and protection in SFTSV mRNA vaccination
npj Vaccines, 2025
Cha I., Yamada Y., Kim D., Kang S., Yang W., Shin W., Ryder A., Lewis M., Chung C., Cho N., Choi Y., Li J., Lai C., Jung J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Mouse Cell Culture Supernatant | O Olink Target 48 Mouse |
Abstract
Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is an emerging tick-borne pathogen with a high case-fatality rate and no approved vaccine, posing a global health threat. Human codon-optimized viral antigens can enhance mRNA vaccine efficacy by improving antigen expression but often requires high mRNA doses, increasing the risk of side effects. In this study, we introduce a codon optimization strategy using Herpes Simplex Virus 1 glycoprotein B (HSVgB) codon usage to develop an mRNA lipid nanoparticle (LNP) vaccine targeting the neutralizing Gn-H domain of SFTSV (sGn-H). The HSVgB codon-optimized mRNA vaccine [sGn-H (HSVgB)] achieved higher antigen expression and elicited stronger humoral and cellular immune responses than a human codon-optimized counterpart [sGn-H (human)]. Notably, sGn-H (HSVgB) induced more bone marrow-resident antibody-secreting cells and conferred superior protection against SFTSV at lower doses. These findings highlight HSVgB codon optimization may represent a promising strategy for enhancing the immunogenicity with low-dose mRNA immunization.