未修饰的狂犬病 mRNA 疫苗可引发高交叉中和抗体滴度和多样化的 B 细胞记忆应答。
Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses.
机构信息
Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Center of Molecular Medicine, Stockholm, Sweden.
出版信息
Nat Commun. 2023 Jun 22;14(1):3713. doi: 10.1038/s41467-023-39421-5.
Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.
基于全灭活病毒的狂犬病许可疫苗在人类中是有效的。然而,对于所引起的免疫反应,以及是否可以使用新型疫苗平台来改善反应,缺乏详细的研究。在这里,我们表明,与两次接种狂犬病疫苗(Rabipur)相比,两剂脂质纳米颗粒配方的未修饰 mRNA 疫苗(编码狂犬病病毒糖蛋白(RABV-G))可在非人类灵长类动物的血液中诱导更高水平的 RABV-G 特异性浆母细胞和 T 细胞,以及骨髓中的浆细胞。mRNA 疫苗还可产生比 Rabipur 更高的 RABV-G 结合和中和抗体滴度,而两种疫苗的反应的体细胞超突变和克隆多样性程度相似。mRNA 疫苗诱导的总体抗体滴度提高转化为相关狂犬病病毒株的交叉中和作用得到改善,这表明该平台具有针对这些病毒开发广泛保护疫苗的潜力。