Complexing CpG adjuvants with cationic liposomes enhances vaccine-induced formation of liver T RM cells.

Tissue resident memory T cells (T _RM cells) can provide effective tissue surveillance and can respond rapidly to infection. Vaccination strategies aimed at generating T _RM cells have shown promise against a range of pathogens. We have previously shown that the choice of adjuvant critically influences CD8 ⁺ T _RM 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 _RM formation in a subunit vaccination model. We show that CpG oligodeoxynucleotides (ODN) remain the most efficient inducers of liver T _RM 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 _RM -based vaccines for their potential translation.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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