Synthetic melanin bound to subunit vaccine antigens significantly enhances CD8+ T-cell responses
Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin...
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| Veröffentlicht in: | PloS one 2017-07, Vol.12 (7), p.e0181403-e0181403 |
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| creator | Carpentier, Antoine F Geinguenaud, Frédéric Tran, Thi Sejalon, Floraly Martin, Antoine Motte, Laurence Tartour, Eric Banissi, Claire |
| description | Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides. Immunization with melanin-bound peptides efficiently triggered CTL responses in mice, even against self-antigens and at a very low dose of peptides (microgram range). Immunization against a tumor antigen inhibited the growth of established tumors in mice, an effect that was abrogated by the depletion of CD8+ lymphocytes. These results demonstrate the efficacy of melanin as a vaccine adjuvant. |
| doi_str_mv | 10.1371/journal.pone.0181403 |
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Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides. Immunization with melanin-bound peptides efficiently triggered CTL responses in mice, even against self-antigens and at a very low dose of peptides (microgram range). Immunization against a tumor antigen inhibited the growth of established tumors in mice, an effect that was abrogated by the depletion of CD8+ lymphocytes. These results demonstrate the efficacy of melanin as a vaccine adjuvant.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0181403</identifier><identifier>PMID: 28715455</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvants, Immunologic ; Amino acids ; Animals ; Antigens ; Antigens, Neoplasm - chemistry ; Autoantigens ; Biology and Life Sciences ; Cancer ; Cancer Vaccines - chemistry ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cytotoxicity ; Dendritic cells ; Dihydroxyphenylalanine ; Dopa ; Epitopes ; Epitopes, T-Lymphocyte - chemistry ; Epitopes, T-Lymphocyte - immunology ; Female ; Immunity ; Immunization ; Immunologic Memory ; Levodopa ; Life Sciences ; Lymph Nodes - immunology ; Lymph Nodes - pathology ; Lymphatic system ; Lymphocytes ; Lymphocytes T ; Medicine and Health Sciences ; Melanin ; Melanins - chemical synthesis ; Melanins - chemistry ; Melanins - immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nanoparticles ; Neoplasm Transplantation ; Neoplasms - immunology ; Neoplasms - pathology ; Neoplasms - therapy ; Oxidation ; Oxidation-Reduction ; Peptides ; Physical Sciences ; Pigmentation ; Spectrum analysis ; Synthetic peptides ; Tumors ; Vaccines ; Vaccines, Subunit - chemistry ; Vaccines, Subunit - immunology</subject><ispartof>PloS one, 2017-07, Vol.12 (7), p.e0181403-e0181403</ispartof><rights>2017 Carpentier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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pathology</subject><subject>Lymphatic system</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine and Health Sciences</subject><subject>Melanin</subject><subject>Melanins - chemical synthesis</subject><subject>Melanins - chemistry</subject><subject>Melanins - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Nanoparticles</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - pathology</subject><subject>Neoplasms - therapy</subject><subject>Oxidation</subject><subject>Oxidation-Reduction</subject><subject>Peptides</subject><subject>Physical Sciences</subject><subject>Pigmentation</subject><subject>Spectrum analysis</subject><subject>Synthetic peptides</subject><subject>Tumors</subject><subject>Vaccines</subject><subject>Vaccines, Subunit - chemistry</subject><subject>Vaccines, Subunit - immunology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1vEzEQXSEQLYV_gMASFxBKGNvr3fUFqQofrRSJA-Vs_DGbONrYYb0bKf8eh2yrtuJke_zem5mnVxSvKcwpr-mnTRz7oLv5LgacA21oCfxJcU4lZ7OKAX96735WvEhpAyB4U1XPizPW1FSUQpwXv38ewrDGwVuyxU4HH4iJY3BkiCSNZgx-IHttrQ9IdBj8CkMiya-Cb73Nhe5AMKx1sJjI4kvzkdzMLHYd6THlwRKml8WzVncJX03nRfHr29ebxdVs-eP79eJyObOigmHWGFcDZ9oZVzkqWckBayu44WA11oZJZ2zToKQOK-3K2rWGC9FQRANS1vyieHvS3XUxqcmcpKiUVAgomzIjrk8IF_VG7Xq_1f1BRe3Vv0LsV0r32YgOVdVaBrYFZKYuwUjpID-k5q1jHBjLWp-nbqPZorMYhl53D0Qf_gS_Vqu4V0JQLrjMAh9OAutHtKvLpTrWgMsaAMo9zdj3U7M-_hkxDWrr09FlHTCOxx1ZnaeqyiZD3z2C_t-J8oSyfUypx_ZuAgrqGK5bljqGS03hyrQ395e-I92mif8FZpbNzw</recordid><startdate>20170717</startdate><enddate>20170717</enddate><creator>Carpentier, Antoine F</creator><creator>Geinguenaud, Frédéric</creator><creator>Tran, Thi</creator><creator>Sejalon, Floraly</creator><creator>Martin, Antoine</creator><creator>Motte, Laurence</creator><creator>Tartour, Eric</creator><creator>Banissi, Claire</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2926-0060</orcidid><orcidid>https://orcid.org/0000-0001-6129-539X</orcidid></search><sort><creationdate>20170717</creationdate><title>Synthetic melanin bound to subunit vaccine antigens significantly enhances CD8+ T-cell responses</title><author>Carpentier, Antoine F ; Geinguenaud, Frédéric ; Tran, Thi ; Sejalon, Floraly ; Martin, Antoine ; Motte, Laurence ; Tartour, Eric ; Banissi, Claire</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c560t-8bd7032adbd6d192430e7c53b30cae7b29dbc88e91de6ad47dfb35581eeb09973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adjuvants, Immunologic</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Antigens</topic><topic>Antigens, Neoplasm - 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Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides. Immunization with melanin-bound peptides efficiently triggered CTL responses in mice, even against self-antigens and at a very low dose of peptides (microgram range). Immunization against a tumor antigen inhibited the growth of established tumors in mice, an effect that was abrogated by the depletion of CD8+ lymphocytes. These results demonstrate the efficacy of melanin as a vaccine adjuvant.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28715455</pmid><doi>10.1371/journal.pone.0181403</doi><orcidid>https://orcid.org/0000-0003-2926-0060</orcidid><orcidid>https://orcid.org/0000-0001-6129-539X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adjuvants, Immunologic Amino acids Animals Antigens Antigens, Neoplasm - chemistry Autoantigens Biology and Life Sciences Cancer Cancer Vaccines - chemistry CD8 antigen CD8-Positive T-Lymphocytes - immunology Cytotoxicity Dendritic cells Dihydroxyphenylalanine Dopa Epitopes Epitopes, T-Lymphocyte - chemistry Epitopes, T-Lymphocyte - immunology Female Immunity Immunization Immunologic Memory Levodopa Life Sciences Lymph Nodes - immunology Lymph Nodes - pathology Lymphatic system Lymphocytes Lymphocytes T Medicine and Health Sciences Melanin Melanins - chemical synthesis Melanins - chemistry Melanins - immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Nanoparticles Neoplasm Transplantation Neoplasms - immunology Neoplasms - pathology Neoplasms - therapy Oxidation Oxidation-Reduction Peptides Physical Sciences Pigmentation Spectrum analysis Synthetic peptides Tumors Vaccines Vaccines, Subunit - chemistry Vaccines, Subunit - immunology |
| title | Synthetic melanin bound to subunit vaccine antigens significantly enhances CD8+ T-cell responses |
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