Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination
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 a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2012
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| Online Access: | http://hdl.handle.net/1721.1/72523 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1826195397861703680 |
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| author | Olvera-Gomez, Irlanda Hamilton, Sara E. Xiao, Zhengguo Guimaraes, Carla P. Ploegh, Hidde Hogquist, Kristin A. Wang, Liangchun Jameson, Stephen C. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Olvera-Gomez, Irlanda Hamilton, Sara E. Xiao, Zhengguo Guimaraes, Carla P. Ploegh, Hidde Hogquist, Kristin A. Wang, Liangchun Jameson, Stephen C. |
| author_sort | Olvera-Gomez, Irlanda |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:12:01Z |
| format | Article |
| id | mit-1721.1/72523 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:12:01Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/725232022-09-26T16:23:38Z Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination Olvera-Gomez, Irlanda Hamilton, Sara E. Xiao, Zhengguo Guimaraes, Carla P. Ploegh, Hidde Hogquist, Kristin A. Wang, Liangchun Jameson, Stephen C. Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Ploegh, Hidde Ploegh, Hidde 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. 2012-09-05T15:47:29Z 2012-09-05T15:47:29Z 2012-01 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/72523 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 https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1073/pnas.1105771109 Proceedings of the National Academy of Sciences 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. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Olvera-Gomez, Irlanda Hamilton, Sara E. Xiao, Zhengguo Guimaraes, Carla P. Ploegh, Hidde Hogquist, Kristin A. Wang, Liangchun Jameson, Stephen C. Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination |
| title | Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination |
| title_full | Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination |
| title_fullStr | Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination |
| title_full_unstemmed | Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination |
| title_short | Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination |
| title_sort | cholera toxin activates nonconventional adjuvant pathways that induce protective cd8 t cell responses after epicutaneous vaccination |
| url | http://hdl.handle.net/1721.1/72523 https://orcid.org/0000-0002-1090-6071 |
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