Complexing CpG adjuvants with cationic liposomes enhances vaccine-induced formation of liver TRM cells

Ana Maria Valencia-Hernandez, Thomas Zillinger, Zhengyu Ge, Peck S. Tan, Anton Cozijnsen, Geoffrey I. McFadden, Mireille H. Lahoud, Irina Caminschi, Winfried Barchet, William R. Heath, Daniel Fernandez-Ruiz

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Tissue resident memory T cells (TRM cells) can provide effective tissue surveillance and can respond rapidly to infection. Vaccination strategies aimed at generating TRM cells have shown promise against a range of pathogens. We have previously shown that the choice of adjuvant critically influences CD8+ TRM 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+ TRM formation in a subunit vaccination model. We show that CpG oligodeoxynucleotides (ODN) remain the most efficient inducers of liver TRM 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 TRM-based vaccines for their potential translation.

Original languageEnglish
Pages (from-to)1094-1107
Number of pages14
Issue number5
Publication statusPublished - 27 Jan 2023


  • Adjuvants
  • Liver immunology
  • Pattern recognition receptors
  • T cell memory
  • Tissue-resident memory T cells
  • Toll-like receptors
  • type I dendritic cells
  • Vaccination

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