Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination
Name
Olvera-Gomez-2012-Cholera toxin activa.pdf
Size
431.57 KB
Format
Adobe PDF
Checksum (MD5)
c8b6ae44f796d8c33411612777bcf492
Author(s)
Olvera-Gomez, Irlanda
Hamilton, Sara E.
Xiao, Zhengguo
Guimaraes, Carla P.
Ploegh, Hidde
Hogquist, Kristin A.
Wang, Liangchun
Jameson, Stephen C.
Date Issued
January 2012
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Olvera-Gomez, I. et al. “Cholera Toxin Activates Nonconventional Adjuvant Pathways That Induce Protective CD8 T-cell Responses After Epicutaneous Vaccination.” Proceedings of the National Academy of Sciences 109.6 (2012): 2072–2077. Copyright ©2012 by the National Academy of Sciences
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.1105771109
