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

doi:10.1016/j.vaccine.2022.12.047

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

Vaccine. 2023 Jan 27;41(5):1094-1107. doi: 10.1016/j.vaccine.2022.12.047. Epub 2023 Jan 4.

Affiliations

¹ 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.
² Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital of Bonn, Bonn D-53127, Germany.
³ Dept. of Microbiology and Immunology, Peter Doherty Institute, The University of Melbourne, Melbourne, Vic 3000, Australia.
⁴ Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
⁵ School of Biosciences, University of Melbourne, Parkville, Vic 3010, Australia.
⁶ Dept. of Microbiology and Immunology, Peter Doherty Institute, The University of Melbourne, Melbourne, Vic 3000, Australia; Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
⁷ Dept. of Microbiology and Immunology, Peter Doherty Institute, The University of Melbourne, Melbourne, Vic 3000, Australia. Electronic address: wrheath@unimelb.edu.au.
⁸ Dept. of Microbiology and Immunology, Peter Doherty Institute, The University of Melbourne, Melbourne, Vic 3000, Australia. Electronic address: danielfr@unimelb.edu.au.

PMID: 36609029
DOI: 10.1016/j.vaccine.2022.12.047

Abstract

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.

Keywords: Adjuvants; Liver immunology; Pattern recognition receptors; T cell memory; Tissue-resident memory T cells; Toll-like receptors; Vaccination; type I dendritic cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
CD8-Positive T-Lymphocytes
Humans
Liposomes*
Liver
Oligodeoxyribonucleotides / pharmacology
Toll-Like Receptor 9
Vaccines*

Substances

Liposomes
Toll-Like Receptor 9
Adjuvants, Immunologic
Vaccines
Oligodeoxyribonucleotides