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...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2012-02, Vol.109 (6), p.2072-2077 |
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creator | Olvera-Gomez, Irlanda Hamilton, Sara E. Xiao, Zhengguo Guimaraes, Carla P. Ploegh, Hidde L. Hogquist, Kristin A. Wang, Liangchun Jameson, Stephen C. |
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. |
doi_str_mv | 10.1073/pnas.1105771109 |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1105771109</identifier><identifier>PMID: 22308317</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adjuvants, Immunologic - metabolism ; Administration, Cutaneous ; Animals ; Antigens ; Antigens - immunology ; Antigens, Surface - metabolism ; Basic-Leucine Zipper Transcription Factors - metabolism ; Biological Sciences ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; Cells, Cultured ; Cholera ; Cholera Toxin - administration & dosage ; Cholera Toxin - immunology ; Dendritic cells ; G(M1) Ganglioside - immunology ; Immunity ; Immunization ; Immunologic Memory - drug effects ; Interferon Type I - immunology ; Lectins, C-Type - metabolism ; Mannose-Binding Lectins - metabolism ; Mice ; Mice, Inbred C57BL ; Oligodeoxyribonucleotides - pharmacology ; Ova ; Repressor Proteins - metabolism ; Signal Transduction - drug effects ; Signal Transduction - immunology ; Skin ; T cell receptors ; T lymphocytes ; Toll-Like Receptors - immunology ; Toxins ; Vaccination ; Vaccines</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2012-02, Vol.109 (6), p.2072-2077</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 7, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-32a796e82509674fda8cb1e1bbfa03a558ef478da8ce8ed96a801c1bc30e937b3</citedby><cites>FETCH-LOGICAL-c496t-32a796e82509674fda8cb1e1bbfa03a558ef478da8ce8ed96a801c1bc30e937b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/109/6.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41477074$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41477074$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22308317$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olvera-Gomez, Irlanda</creatorcontrib><creatorcontrib>Hamilton, Sara E.</creatorcontrib><creatorcontrib>Xiao, Zhengguo</creatorcontrib><creatorcontrib>Guimaraes, Carla P.</creatorcontrib><creatorcontrib>Ploegh, Hidde L.</creatorcontrib><creatorcontrib>Hogquist, Kristin A.</creatorcontrib><creatorcontrib>Wang, Liangchun</creatorcontrib><creatorcontrib>Jameson, Stephen C.</creatorcontrib><title>Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><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.</description><subject>Adjuvants, Immunologic - metabolism</subject><subject>Administration, Cutaneous</subject><subject>Animals</subject><subject>Antigens</subject><subject>Antigens - immunology</subject><subject>Antigens, Surface - metabolism</subject><subject>Basic-Leucine Zipper Transcription Factors - metabolism</subject><subject>Biological Sciences</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cells, Cultured</subject><subject>Cholera</subject><subject>Cholera Toxin - administration & dosage</subject><subject>Cholera Toxin - immunology</subject><subject>Dendritic cells</subject><subject>G(M1) Ganglioside - immunology</subject><subject>Immunity</subject><subject>Immunization</subject><subject>Immunologic Memory - drug effects</subject><subject>Interferon Type I - immunology</subject><subject>Lectins, C-Type - metabolism</subject><subject>Mannose-Binding Lectins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Oligodeoxyribonucleotides - pharmacology</subject><subject>Ova</subject><subject>Repressor Proteins - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - immunology</subject><subject>Skin</subject><subject>T cell receptors</subject><subject>T lymphocytes</subject><subject>Toll-Like Receptors - immunology</subject><subject>Toxins</subject><subject>Vaccination</subject><subject>Vaccines</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc-P1CAYhhujccfVsycN8eKpu0BpoReTzfgz2cTLeiZf6VeHSQcq0Ore_cOlmXV29QIJPN8TXt6ieMnoBaOyupwcxAvGaC1lXttHxSavrGxESx8XG0q5LJXg4qx4FuOeUtrWij4tzjivqKqY3BS_tzs_YgCS_C_rCJhkF0gYifPOeLegS9Y7GAn0-3kBl8gEafcTbiNJO0jEun42SKbgE66zSLbvFbkpDY4jCRgn72K2wZAwEJysmRM49HMkCxhjHaz658WTAcaIL-728-Lbxw8328_l9ddPX7ZX16URbZPKioNsG1S8pm0jxdCDMh1D1nUD0ArqWuEgpFqPUWHfNqAoM6wzFcW2kl11Xrw7eqe5O2BvcrgAo56CPUC41R6s_vfG2Z3-7hddcSmzPgve3gmC_zFjTPpg4xr1mEm3jWKNbJjI5Jv_yL2fQ_7IDHFGqaibOkOXR8gEH2PA4fQURvXar1771ff95onXDxOc-L-FPgDWyXtdqxvNqeQZeHUE9jH5cCIEE1JSKao_sRC5lQ</recordid><startdate>20120207</startdate><enddate>20120207</enddate><creator>Olvera-Gomez, Irlanda</creator><creator>Hamilton, Sara E.</creator><creator>Xiao, Zhengguo</creator><creator>Guimaraes, Carla P.</creator><creator>Ploegh, Hidde L.</creator><creator>Hogquist, Kristin A.</creator><creator>Wang, Liangchun</creator><creator>Jameson, Stephen C.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20120207</creationdate><title>Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination</title><author>Olvera-Gomez, Irlanda ; 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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22308317</pmid><doi>10.1073/pnas.1105771109</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adjuvants, Immunologic - metabolism Administration, Cutaneous Animals Antigens Antigens - immunology Antigens, Surface - metabolism Basic-Leucine Zipper Transcription Factors - metabolism Biological Sciences CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology Cells, Cultured Cholera Cholera Toxin - administration & dosage Cholera Toxin - immunology Dendritic cells G(M1) Ganglioside - immunology Immunity Immunization Immunologic Memory - drug effects Interferon Type I - immunology Lectins, C-Type - metabolism Mannose-Binding Lectins - metabolism Mice Mice, Inbred C57BL Oligodeoxyribonucleotides - pharmacology Ova Repressor Proteins - metabolism Signal Transduction - drug effects Signal Transduction - immunology Skin T cell receptors T lymphocytes Toll-Like Receptors - immunology Toxins Vaccination Vaccines |
title | Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination |
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