An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response
Abstract We investigated whether a combined DNA vaccine delivered together with the IL-15 gene (DNA- IL-15 (+)) enhanced the immune response against Brucella abortus in mice. Mice vaccinated with DNA-IL-15(+) developed a robust humoral response; Brucella -specific antibodies exhibited a dominance of...
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| Veröffentlicht in: | Vaccine 2010-03, Vol.28 (12), p.2408-2415 |
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| creator | Hu, Xi-Dan Chen, Su-Ting Li, Jia-Yun Yu, Da-Hai Yi-zhang Cai, Hong |
| description | Abstract We investigated whether a combined DNA vaccine delivered together with the IL-15 gene (DNA- IL-15 (+)) enhanced the immune response against Brucella abortus in mice. Mice vaccinated with DNA-IL-15(+) developed a robust humoral response; Brucella -specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. Splenocytes from DNA-IL-15(+)-vaccinated mice induced significantly higher levels of IFN-γ ( P < 0.01) and CD8+ T cell response ( P < 0.01), suggesting induction of a T-helper-1-dominated immune response. In a specific cytotoxic-T-lymphocyte activity assay, DNA-IL-15(+) immunization elicited mainly CD8+ T cells, which mediate cytotoxicity, but also CD4+ T cells. In vivo depletion of T cell subsets showed that the DNA-IL-15(+)-induced protection against Brucella infection is mediated predominantly by CD8+ T cells, although CD4+ T cells also contribute. These data indicate that plasmid-delivered IL-15 increases the efficacy of the Brucella DNA vaccine. |
| doi_str_mv | 10.1016/j.vaccine.2009.12.076 |
| format | Article |
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Mice vaccinated with DNA-IL-15(+) developed a robust humoral response; Brucella -specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. Splenocytes from DNA-IL-15(+)-vaccinated mice induced significantly higher levels of IFN-γ ( P < 0.01) and CD8+ T cell response ( P < 0.01), suggesting induction of a T-helper-1-dominated immune response. In a specific cytotoxic-T-lymphocyte activity assay, DNA-IL-15(+) immunization elicited mainly CD8+ T cells, which mediate cytotoxicity, but also CD4+ T cells. In vivo depletion of T cell subsets showed that the DNA-IL-15(+)-induced protection against Brucella infection is mediated predominantly by CD8+ T cells, although CD4+ T cells also contribute. These data indicate that plasmid-delivered IL-15 increases the efficacy of the Brucella DNA vaccine.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2009.12.076</identifier><identifier>PMID: 20064480</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Abortion ; Adjuvants, Immunologic - administration & dosage ; Allergy and Immunology ; Animals ; Antibodies, Bacterial - blood ; Applied microbiology ; Bacteria ; Bacteriology ; Biological and medical sciences ; Brucella abortus ; Brucella abortus - genetics ; Brucella abortus - immunology ; Brucella Vaccine - genetics ; Brucella Vaccine - immunology ; Brucellosis ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - immunology ; Cloning ; Combined DNA vaccine ; Cytotoxicity ; Cytotoxicity Tests, Immunologic ; Deoxyribonucleic acid ; DNA ; Enzymes ; Female ; Fundamental and applied biological sciences. Psychology ; Genes ; Immune response ; Immunization ; Immunoglobulin G - blood ; Interferon-gamma - secretion ; Interleukin-15 - administration & dosage ; Interleukin-15 - genetics ; Interleukin-4 - secretion ; Lymphocyte Depletion ; Lymphocytes ; Mice ; Mice, Inbred BALB C ; Microbiology ; Miscellaneous ; Plasmids ; Protective immunity ; Spleen ; Spleen - immunology ; Spleen - pathology ; T-Lymphocyte Subsets - immunology ; T-Lymphocytes, Cytotoxic - immunology ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) ; Vaccines, DNA - immunology</subject><ispartof>Vaccine, 2010-03, Vol.28 (12), p.2408-2415</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Elsevier Limited Mar 11, 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-f571ea8b21f2e6cf5283efab34fd2312c566a8526dd7bbc230adf580c2c0a2dd3</citedby><cites>FETCH-LOGICAL-c477t-f571ea8b21f2e6cf5283efab34fd2312c566a8526dd7bbc230adf580c2c0a2dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X10000125$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22520487$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20064480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Xi-Dan</creatorcontrib><creatorcontrib>Chen, Su-Ting</creatorcontrib><creatorcontrib>Li, Jia-Yun</creatorcontrib><creatorcontrib>Yu, Da-Hai</creatorcontrib><creatorcontrib>Yi-zhang</creatorcontrib><creatorcontrib>Cai, Hong</creatorcontrib><title>An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract We investigated whether a combined DNA vaccine delivered together with the IL-15 gene (DNA- IL-15 (+)) enhanced the immune response against Brucella abortus in mice. Mice vaccinated with DNA-IL-15(+) developed a robust humoral response; Brucella -specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. Splenocytes from DNA-IL-15(+)-vaccinated mice induced significantly higher levels of IFN-γ ( P < 0.01) and CD8+ T cell response ( P < 0.01), suggesting induction of a T-helper-1-dominated immune response. In a specific cytotoxic-T-lymphocyte activity assay, DNA-IL-15(+) immunization elicited mainly CD8+ T cells, which mediate cytotoxicity, but also CD4+ T cells. In vivo depletion of T cell subsets showed that the DNA-IL-15(+)-induced protection against Brucella infection is mediated predominantly by CD8+ T cells, although CD4+ T cells also contribute. These data indicate that plasmid-delivered IL-15 increases the efficacy of the Brucella DNA vaccine.</description><subject>Abortion</subject><subject>Adjuvants, Immunologic - administration & dosage</subject><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Antibodies, Bacterial - blood</subject><subject>Applied microbiology</subject><subject>Bacteria</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>Brucella abortus</subject><subject>Brucella abortus - genetics</subject><subject>Brucella abortus - immunology</subject><subject>Brucella Vaccine - genetics</subject><subject>Brucella Vaccine - immunology</subject><subject>Brucellosis</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cloning</subject><subject>Combined DNA vaccine</subject><subject>Cytotoxicity</subject><subject>Cytotoxicity Tests, Immunologic</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Enzymes</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes</subject><subject>Immune response</subject><subject>Immunization</subject><subject>Immunoglobulin G - blood</subject><subject>Interferon-gamma - secretion</subject><subject>Interleukin-15 - administration & dosage</subject><subject>Interleukin-15 - genetics</subject><subject>Interleukin-4 - secretion</subject><subject>Lymphocyte Depletion</subject><subject>Lymphocytes</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Plasmids</subject><subject>Protective immunity</subject><subject>Spleen</subject><subject>Spleen - immunology</subject><subject>Spleen - pathology</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><subject>Vaccines, DNA - immunology</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkk1vEzEQhi0EoiHwE0CWEOKANvhz17mAQspHpQgOFImb5bXHrcPGG-zdiJz54zhNoFIvnHx55p3xPIPQU0pmlND69Xq2M9aGCDNGyHxG2Yw09T00oarhFZNU3UcTwmpRCUq-n6FHOa8JIZLT-UN0VkpqIRSZoN-LiC9WFZXYuPW4M3HAEK9NtJDxcA0YvA_W2D3uPTbY9pu2tHT4_PMCn_pjc2VCzAN-l0YLXWdwu8ch2gQmh3h1k7I8V6-w3Q_90P8KFl_iA4gT5G0fMzxGD7zpMjw5vVP07cP7y-WnavXl48VysaqsaJqh8rKhYFTLqGdQWy-Z4uBNy4V3jFNmZV0bJVntXNO2lnFinJeKWGaJYc7xKXp5zN2m_ucIedCbkG9GjtCPWTecS65qpQr5_A657scUy3CairkSggohCyWPlE19zgm83qawMWmvKdEHSXqtT0vSB0maMl0klbpnp_Sx3YD7V_XXSgFenACTrel8Kj5CvuWYZEQUz1P09shB2douQNLZBijuXEhgB-368N9R3txJsF2IxXj3A_aQb3-tcynQXw8XdTgoWm6JUCb5HwydxoY</recordid><startdate>20100311</startdate><enddate>20100311</enddate><creator>Hu, Xi-Dan</creator><creator>Chen, Su-Ting</creator><creator>Li, Jia-Yun</creator><creator>Yu, Da-Hai</creator><creator>Yi-zhang</creator><creator>Cai, Hong</creator><general>Elsevier Ltd</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><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>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20100311</creationdate><title>An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response</title><author>Hu, Xi-Dan ; Chen, Su-Ting ; Li, Jia-Yun ; Yu, Da-Hai ; Yi-zhang ; Cai, Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-f571ea8b21f2e6cf5283efab34fd2312c566a8526dd7bbc230adf580c2c0a2dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Abortion</topic><topic>Adjuvants, Immunologic - administration & dosage</topic><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Antibodies, Bacterial - blood</topic><topic>Applied microbiology</topic><topic>Bacteria</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>Brucella abortus</topic><topic>Brucella abortus - genetics</topic><topic>Brucella abortus - immunology</topic><topic>Brucella Vaccine - genetics</topic><topic>Brucella Vaccine - immunology</topic><topic>Brucellosis</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cloning</topic><topic>Combined DNA vaccine</topic><topic>Cytotoxicity</topic><topic>Cytotoxicity Tests, Immunologic</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Enzymes</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes</topic><topic>Immune response</topic><topic>Immunization</topic><topic>Immunoglobulin G - blood</topic><topic>Interferon-gamma - secretion</topic><topic>Interleukin-15 - administration & dosage</topic><topic>Interleukin-15 - genetics</topic><topic>Interleukin-4 - secretion</topic><topic>Lymphocyte Depletion</topic><topic>Lymphocytes</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Plasmids</topic><topic>Protective immunity</topic><topic>Spleen</topic><topic>Spleen - immunology</topic><topic>Spleen - pathology</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Vaccines</topic><topic>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</topic><topic>Vaccines, DNA - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Xi-Dan</creatorcontrib><creatorcontrib>Chen, Su-Ting</creatorcontrib><creatorcontrib>Li, Jia-Yun</creatorcontrib><creatorcontrib>Yu, Da-Hai</creatorcontrib><creatorcontrib>Yi-zhang</creatorcontrib><creatorcontrib>Cai, Hong</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Xi-Dan</au><au>Chen, Su-Ting</au><au>Li, Jia-Yun</au><au>Yu, Da-Hai</au><au>Yi-zhang</au><au>Cai, Hong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2010-03-11</date><risdate>2010</risdate><volume>28</volume><issue>12</issue><spage>2408</spage><epage>2415</epage><pages>2408-2415</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><coden>VACCDE</coden><abstract>Abstract We investigated whether a combined DNA vaccine delivered together with the IL-15 gene (DNA- IL-15 (+)) enhanced the immune response against Brucella abortus in mice. Mice vaccinated with DNA-IL-15(+) developed a robust humoral response; Brucella -specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. Splenocytes from DNA-IL-15(+)-vaccinated mice induced significantly higher levels of IFN-γ ( P < 0.01) and CD8+ T cell response ( P < 0.01), suggesting induction of a T-helper-1-dominated immune response. In a specific cytotoxic-T-lymphocyte activity assay, DNA-IL-15(+) immunization elicited mainly CD8+ T cells, which mediate cytotoxicity, but also CD4+ T cells. In vivo depletion of T cell subsets showed that the DNA-IL-15(+)-induced protection against Brucella infection is mediated predominantly by CD8+ T cells, although CD4+ T cells also contribute. These data indicate that plasmid-delivered IL-15 increases the efficacy of the Brucella DNA vaccine.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>20064480</pmid><doi>10.1016/j.vaccine.2009.12.076</doi><tpages>8</tpages></addata></record> |
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| subjects | Abortion Adjuvants, Immunologic - administration & dosage Allergy and Immunology Animals Antibodies, Bacterial - blood Applied microbiology Bacteria Bacteriology Biological and medical sciences Brucella abortus Brucella abortus - genetics Brucella abortus - immunology Brucella Vaccine - genetics Brucella Vaccine - immunology Brucellosis CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Cloning Combined DNA vaccine Cytotoxicity Cytotoxicity Tests, Immunologic Deoxyribonucleic acid DNA Enzymes Female Fundamental and applied biological sciences. Psychology Genes Immune response Immunization Immunoglobulin G - blood Interferon-gamma - secretion Interleukin-15 - administration & dosage Interleukin-15 - genetics Interleukin-4 - secretion Lymphocyte Depletion Lymphocytes Mice Mice, Inbred BALB C Microbiology Miscellaneous Plasmids Protective immunity Spleen Spleen - immunology Spleen - pathology T-Lymphocyte Subsets - immunology T-Lymphocytes, Cytotoxic - immunology Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) Vaccines, DNA - immunology |
| title | An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response |
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