Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, 3010, Australia.
Eur J Immunol. 2021 May;51(5):1153-1165. doi: 10.1002/eji.202048757. Epub 2021 Feb 12.
Malaria remains a major cause of mortality in the world and an efficient vaccine is the best chance of reducing the disease burden. Vaccination strategies for the liver stage of disease that utilise injection of live radiation-attenuated sporozoites (RAS) confer sterile immunity, which is mediated by CD8 memory T cells, with liver-resident memory T cells (T ) being particularly important. We have previously described a TCR transgenic mouse, termed PbT-I, where all CD8 T cells recognize a specific peptide from Plasmodium. PbT-I form liver T cells upon RAS injection and are capable of protecting mice against challenge infection. Here, we utilize this transgenic system to examine whether nonliving sporozoites, killed by heat treatment (HKS), could trigger the development of Plasmodium-specific liver T cells. We found that HKS vaccination induced the formation of memory CD8 T cells in the spleen and liver, and importantly, liver T cells were fewer in number than that induced by RAS. Crucially, we showed the number of T cells was significantly higher when HKS were combined with the glycolipid α-galactosylceramide as an adjuvant. In the future, this work could lead to development of an antimalaria vaccination strategy that does not require live sporozoites, providing greater utility.
疟疾仍然是世界上主要的死亡原因，而有效的疫苗是减轻疾病负担的最佳机会。利用注射活减毒孢子（RAS）来针对疾病的肝脏阶段的疫苗接种策略提供了无菌免疫，这是由 CD8 记忆 T 细胞介导的，肝驻留记忆 T 细胞（T）尤为重要。我们之前描述了一种称为 PbT-I 的 TCR 转基因小鼠，其中所有 CD8 T 细胞都识别来自疟原虫的特定肽。PbT-I 在 RAS 注射后形成肝脏 T 细胞，并能够保护小鼠免受挑战感染。在这里，我们利用这个转基因系统来检查非生活孢子，通过热处理（HKS）杀死，是否可以引发针对疟原虫特异性肝脏 T 细胞的发育。我们发现 HKS 疫苗接种可诱导脾和肝中记忆 CD8 T 细胞的形成，重要的是，肝脏 T 细胞的数量比 RAS 诱导的少。至关重要的是，我们表明当 HKS 与糖脂α-半乳糖神经酰胺作为佐剂结合使用时，T 细胞的数量显著增加。在未来，这项工作可能会导致开发不需要活孢子的抗疟疾疫苗接种策略，从而提供更大的效用。
