DataSheet_1_An mRNA vaccine against rabies provides strong and durable protection in mice.docx

IntroductionRabies is a serious public health problem worldwide for which an effective treatment method is lacking but can be prevented by vaccines. Current vaccines are produced in cell or egg cultures, which are both costly and time consuming.
MethodsHere, a non-replicating mRNA vaccine (RV021) encoding the rabies virus glycoprotein was developed in vitro, and its immunogenicity and protective efficacy against live virus was evaluated in mice.
ResultsA two-dose vaccination with 1 μg of RV021 at 7-day intervals induced a protective level of neutralizing antibody that was maintained for at least 260 days. RV021 induced a robust cellular immune response that was significantly superior to that of an inactivated vaccine. Two doses of 1 μg RV021 provided full protection against challenge with CVS of 30~60-fold lethal dose, 50%. Vaccine potency testing (according to the National Institutes of Health) in vivo revealed that the potency of RV021 at 15 μg/dose was 7.5 IU/dose, which is substantially higher than the standard for lot release of rabies vaccines for current human use.
ConclusionThe mRNA vaccine RV021 induces a strong protective immune response in mice, providing a new and promising strategy for human rabies prevention and control.

引言
狂犬病是全球范围内亟待防控的重大公共卫生问题，目前尚无特效治疗手段，但可通过疫苗接种实现有效预防。现有疫苗多通过细胞培养或鸡胚培养工艺生产，不仅成本高昂，且制备周期冗长。

方法
本研究体外研发了一款编码狂犬病病毒糖蛋白的非复制型mRNA疫苗（mRNA vaccine）RV021，并在小鼠模型中评估了其免疫原性与活病毒攻击后的保护效力。

结果
以1 μg剂量、间隔7天接种两剂RV021，可诱导出保护性水平的中和抗体，且该抗体滴度至少可维持260天。RV021可引发强烈的细胞免疫应答，其效果显著优于传统灭活疫苗。两剂1 μg剂量的RV021可使小鼠完全抵御30~60倍半数致死量（LD₅₀）的CVS毒株（Challenge Virus Standard）攻击。依据美国国立卫生研究院（National Institutes of Health，NIH）标准开展的体内疫苗效价检测显示，15 μg/剂的RV021效价可达7.5 IU/剂，远高于当前人用狂犬病疫苗的批签发效价标准。

结论
mRNA疫苗RV021可在小鼠体内诱导强效的保护性免疫应答，为人类狂犬病的预防与控制提供了全新且极具应用前景的防控策略。