Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination
Open Access
- 23 January 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (6), 2072-2077
- https://doi.org/10.1073/pnas.1105771109
Abstract
The ability to induce humoral and cellular immunity via antigen delivery through the unbroken skin (epicutaneous immunization, EPI) has immediate relevance for vaccine development. However, it is unclear which adjuvants induce protective memory CD8 T-cell responses by this route, and the molecular and cellular requirements for priming through intact skin are not defined. We report that cholera toxin (CT) is superior to other adjuvants in its ability to prime memory CD8 T cells that control bacterial and viral challenges. Epicutaneous immunization with CT does not require engagement of classic toll-like receptor (TLR) and inflammasome pathways and, surprisingly, is independent of skin langerin-expressing cells (including Langerhans cells). However, CT adjuvanticity required type-I IFN sensitivity, participation of a Batf3-dependent dendritic cell (DC) population and engagement of CT with suitable gangliosides. Chemoenzymatic generation of CT–antigen fusion proteins led to efficient priming of the CD8 T-cell responses, paving the way for development of this immunization strategy as a therapeutic option.Keywords
This publication has 51 references indexed in Scilit:
- Identification of host cell factors required for intoxication through use of modified cholera toxinThe Journal of cell biology, 2011
- Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cellsThe Journal of Experimental Medicine, 2011
- Type I interferon is selectively required by dendritic cells for immune rejection of tumorsThe Journal of Experimental Medicine, 2011
- Langerhans cells and dermal dendritic cells capture protein antigens in the skin: Possible targets for vaccination through the skinImmunobiology, 2010
- The role of pattern-recognition receptors in innate immunity: update on Toll-like receptorsNature Immunology, 2010
- Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cellsThe Journal of Experimental Medicine, 2010
- Langerhans cells and more: langerin‐expressing dendritic cell subsets in the skinImmunological Reviews, 2010
- The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansionThe Journal of Experimental Medicine, 2009
- Identification of a novel population of Langerin+ dendritic cellsThe Journal of Experimental Medicine, 2007
- Langerhans cells cross-present antigen derived from skinProceedings of the National Academy of Sciences of the United States of America, 2006