未经证实:狂犬病是一种致命的人畜共患疾病,每年约有60,000人死亡。虽然有灭活狂犬病疫苗,多剂量方案推荐用于暴露前预防或暴露后预防,这降低了成本和时间效率,尤其是在中低收入国家。
UNASSIGNED:我们开发了一种核苷修饰的狂犬病mRNA-脂质纳米颗粒疫苗(RABV-GmRNA-LNP),编码密码子优化的病毒糖蛋白,并与市售灭活疫苗相比,评估了该疫苗在小鼠中的免疫原性和保护功效。
未经授权:我们首先表明,当在小鼠中评估时,与接种三次灭活疫苗相比,单次接种中等或高剂量的RABV-GmRNA可诱导更有效的体液和T细胞免疫应答.重要的是,接受RABV-GmRNA单次免疫的小鼠,即使是低剂量,对致命的狂犬病挑战表现出充分的保护。我们进一步证明,小鼠单次接种RABV-GmRNA诱导的体液免疫应答可持续至少25周,而双剂量策略可以将高度保护性反应的持续时间延长至一年甚至更长。相比之下,灭活疫苗的三剂方案未能做到这一点.
UNASSIGNED:我们的研究证实,值得开发单剂量核苷修饰的狂犬病mRNA-LNP疫苗,这可以提供更长时间和更有效的保护。
Rabies is a lethal zoonotic disease that kills approximately 60,000 people each year. Although inactivated rabies vaccines are available, multiple-dose regimensare recommended for pre-exposure prophylaxis or post-exposure prophylaxis,which cuts down the cost- and time-effectiveness, especially in low- and middle incomecountries.
We developed a nucleoside-modified Rabies mRNA-lipid nanoparticle vaccine (RABV-G mRNA-LNP) encoding codon-optimized viral glycoprotein and assessed the immunogenicity and protective efficacy of this vaccine in mice comparing to a commercially available inactivated vaccine.
We first showed that, when evaluated in mice, a single vaccination of RABV-G mRNA with a moderate or high dose induces more potent humoral and T-cell immune responses than that elicited by three inoculations of the inactivated vaccine. Importantly, mice receiving a single immunization of RABV-G mRNA, even at low doses, showed full protection against the lethal rabies challenge. We further demonstrated that the humoral immune response induced by single RABV-G mRNA vaccination in mice could last for at least 25 weeks, while a two-dose strategy could extend the duration of the highly protective response to one year or even longer. In contrast, the three-dose regimen of inactivated vaccine failed to do so.
Our study confirmed that it is worth developing a single-dose nucleoside-modified Rabies mRNA-LNP vaccine, which could confer much prolonged and more effective protection.