Ferrier Research Institute, Victoria University of Wellington, Lower Hutt, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.
Nat Immunol. 2023 Sep;24(9):1487-1498. doi: 10.1038/s41590-023-01562-6. Epub 2023 Jul 20.
Malaria is caused by Plasmodium species transmitted by Anopheles mosquitoes. Following a mosquito bite, Plasmodium sporozoites migrate from skin to liver, where extensive replication occurs, emerging later as merozoites that can infect red blood cells and cause symptoms of disease. As liver tissue-resident memory T cells (Trm cells) have recently been shown to control liver-stage infections, we embarked on a messenger RNA (mRNA)-based vaccine strategy to induce liver Trm cells to prevent malaria. Although a standard mRNA vaccine was unable to generate liver Trm or protect against challenge with Plasmodium berghei sporozoites in mice, addition of an agonist that recruits T cell help from type I natural killer T cells under mRNA-vaccination conditions resulted in significant generation of liver Trm cells and effective protection. Moreover, whereas previous exposure of mice to blood-stage infection impaired traditional vaccines based on attenuated sporozoites, mRNA vaccination was unaffected, underlining the potential for such a rational mRNA-based strategy in malaria-endemic regions.
疟疾是由疟原虫属通过按蚊传播引起的。被蚊子叮咬后，疟原虫孢子从皮肤迁移到肝脏，在肝脏中大量复制，随后作为能够感染红细胞并引起疾病症状的裂殖子出现。由于肝组织驻留记忆 T 细胞（Trm 细胞）最近被证明可以控制肝期感染，我们着手进行基于信使 RNA（mRNA）的疫苗策略，以诱导肝 Trm 细胞来预防疟疾。尽管标准的 mRNA 疫苗不能在小鼠中产生肝 Trm 细胞或预防疟原虫伯氏疟原虫孢子的挑战，但在 mRNA 疫苗接种条件下添加一种激动剂，从 I 型自然杀伤 T 细胞募集 T 细胞辅助，可显著产生肝 Trm 细胞并有效保护。此外，尽管先前的小鼠血期感染会削弱基于减毒孢子的传统疫苗，但 mRNA 疫苗接种不受影响，这凸显了这种合理的基于 mRNA 的策略在疟疾流行地区的潜力。
