Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses

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. *Here in this Bioproject, all the raw B cell receptor Illumina sequencing files used in this project were included.

基于全灭活病毒的获批狂犬病疫苗对人类具有保护效力。然而，目前尚无针对其诱导的免疫应答的详细研究，也不清楚能否通过新型疫苗平台优化此类免疫应答。本研究证实，在非人灵长类动物中，相较于两剂次的瑞必补尔（Rabipur）疫苗，两剂次编码狂犬病病毒糖蛋白（rabies virus glycoprotein, RABV-G）的脂质纳米颗粒递送未修饰mRNA疫苗，可诱导血液中更高水平的RABV-G特异性浆母细胞与T细胞，以及骨髓中更多的浆细胞。该mRNA疫苗的RABV-G结合抗体效价与中和抗体效价也高于瑞必补尔，而两种疫苗诱导的免疫应答的体细胞高频突变程度与克隆多样性相似。mRNA疫苗诱导的整体抗体效价更高，这使其对相关狂犬病毒属（lyssavirus）毒株的交叉中和活性得到提升，提示该疫苗平台具备开发广谱保护性疫苗以对抗这类病毒的潜力。*本生物项目（BioProject）收录了本研究使用的全部B细胞受体Illumina测序原始文件。