Supporting data for “Novel RNA Adjuvant for Intradermal Influenza and COVID-19 Vaccine”

In this project, we first established a mouse model with optimal virus inoculum and vaccine dosage to screen intradermal adjuvants. Next, we determined whether the combination of TLR9 and TLR7 agonists has superior adjuvant efficacy than TLR9 alone or TLR7 alone. Finally, we tested the efficacy of a novel RNA adjuvant, R266, an RNA derived from the 5’ untranslated region of the SARS-CoV-2 genomic sequence. R266 can improve the survival rate of mice infected with a lethal dose of influenza virus even when only one-sixth of the dose of previous influenza vaccines was immunized. We demonstrated the mechanism of R266 from B cell response and T cell response of mice and found that a powerful T cell response in the early stages of infection might be one key factor in increasing vaccine protection.In conclusion, we demonstrated that R266 could be used as a promising intradermal adjuvant to enhance the effectiveness of the influenza vaccine. Further detailed mechanisms of R266 are worth exploring, which will lay the foundation for future innovations in RNA adjuvants and vaccines.

在本研究中，我们首先建立了具有最佳病毒接种量和疫苗剂量的小鼠模型，用于筛选皮内佐剂。接下来，我们探究了TLR9（Toll-like receptor 9）与TLR7（Toll-like receptor 7）激动剂的组合是否比单独使用TLR9或TLR7具有更优的佐剂效果。最后，我们测试了一种新型RNA佐剂R266的功效——该RNA源自SARS-CoV-2基因组序列的5'非翻译区。即使仅免疫先前流感疫苗剂量的六分之一，R266仍可提高感染致死剂量流感病毒小鼠的存活率。我们从小鼠的B细胞应答和T细胞应答层面阐明了R266的作用机制，并发现感染早期的强效T细胞应答可能是提升疫苗保护力的关键因素之一。综上，我们证实R266可作为极具潜力的皮内佐剂，增强流感疫苗的效力。R266更详尽的作用机制值得深入探究，这将为未来RNA佐剂和疫苗的创新奠定基础。