Valencia-Hernandez Ana Maria, Zillinger Thomas, Ge Zhengyu, Tan Peck S, Cozijnsen Anton, I McFadden Geoffrey, Lahoud Mireille H, Caminschi Irina, Barchet Winfried, Heath William R, Fernandez-Ruiz Daniel
Dept. of Microbiology and Immunology, Peter Doherty Institute, The University of Melbourne, Melbourne, Vic 3000, Australia; Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital of Bonn, Bonn D-53127, Germany.
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital of Bonn, Bonn D-53127, Germany.
Vaccine. 2023 Jan 27;41(5):1094-1107. doi: 10.1016/j.vaccine.2022.12.047. Epub 2023 Jan 4.
Tissue resident memory T cells (T cells) can provide effective tissue surveillance and can respond rapidly to infection. Vaccination strategies aimed at generating T cells have shown promise against a range of pathogens. We have previously shown that the choice of adjuvant critically influences CD8 T cell formation in the liver. However, the range of adjuvants tested was limited. Here, we assessed the ability of a broad range of adjuvants stimulating membrane (TLR4), endosomal (TLR3, TLR7 and TLR9) and cytosolic (cGAS, RIG-I) pathogen recognition receptors for their capacity to induce CD8 T formation in a subunit vaccination model. We show that CpG oligodeoxynucleotides (ODN) remain the most efficient inducers of liver T cells among all adjuvants tested. Moreover, their combination with the cationic liposome DOTAP further enhances the potency, particularly of the class B ODN CpG 1668 and the human TLR9 ligand CpG 2006 (CpG 7909). This study informs the design of efficient liver T-based vaccines for their potential translation.
组织驻留记忆性T细胞（T细胞）可提供有效的组织监测，并能对感染迅速做出反应。旨在产生T细胞的疫苗接种策略已显示出对一系列病原体的防治前景。我们之前已经表明，佐剂的选择对肝脏中CD8 T细胞的形成有至关重要的影响。然而，所测试的佐剂范围有限。在此，我们评估了一系列刺激膜（TLR4）、内体（TLR3、TLR7和TLR9）和胞质（cGAS、RIG-I）病原体识别受体的佐剂在亚单位疫苗接种模型中诱导CD8 T细胞形成的能力。我们表明，在所有测试的佐剂中，CpG寡脱氧核苷酸（ODN）仍然是肝脏T细胞最有效的诱导剂。此外，它们与阳离子脂质体DOTAP的组合进一步增强了效力，特别是B类ODN CpG 1668和人TLR9配体CpG 2006（CpG 7909）。这项研究为基于肝脏T细胞的高效疫苗设计提供了信息，以便其有可能转化应用。
