Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning
Abstract To identify Mycobacterium tuberculosis (Mtb) antigens as candidates for a subunit vaccine against tuberculosis (TB), we have employed a CD4+ T-cell expression screening method. Mtb-specific CD4+ T-cell lines from nine healthy PPD positive donors were stimulated with different antigenic subs...
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creator | Coler, Rhea N Dillon, Davin C Skeiky, Yasir A.W Kahn, Maria Orme, Ian M Lobet, Yves Reed, Steven G Alderson, Mark R |
description | Abstract To identify Mycobacterium tuberculosis (Mtb) antigens as candidates for a subunit vaccine against tuberculosis (TB), we have employed a CD4+ T-cell expression screening method. Mtb-specific CD4+ T-cell lines from nine healthy PPD positive donors were stimulated with different antigenic substrates including autologous dendritic cells (DC) infected with Mtb, or cultured with culture filtrate proteins (CFP), and purified protein derivative of Mtb (PPD). These lines were used to screen a genomic Mtb library expressed in Escherichia coli and processed and presented by autologous DC. This screening led to the recovery of numerous T-cell antigens, including both novel and previously described antigens. One of these novel antigens, referred to as Mtb9.8 (Rv0287), was recognized by multiple T-cell lines, stimulated with either Mtb-infected DC or CFP. Using the mouse and guinea pig models of TB, high levels of IFN-γ were produced, and solid protection from Mtb challenge was observed following immunization with Mtb9.8 formulated in either AS02A or AS01B Adjuvant Systems. These results demonstrate that T-cell screening of the Mtb genome can be used to identify CD4+ T-cell antigens that are candidates for vaccine development. |
doi_str_mv | 10.1016/j.vaccine.2008.10.056 |
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Mtb-specific CD4+ T-cell lines from nine healthy PPD positive donors were stimulated with different antigenic substrates including autologous dendritic cells (DC) infected with Mtb, or cultured with culture filtrate proteins (CFP), and purified protein derivative of Mtb (PPD). These lines were used to screen a genomic Mtb library expressed in Escherichia coli and processed and presented by autologous DC. This screening led to the recovery of numerous T-cell antigens, including both novel and previously described antigens. One of these novel antigens, referred to as Mtb9.8 (Rv0287), was recognized by multiple T-cell lines, stimulated with either Mtb-infected DC or CFP. Using the mouse and guinea pig models of TB, high levels of IFN-γ were produced, and solid protection from Mtb challenge was observed following immunization with Mtb9.8 formulated in either AS02A or AS01B Adjuvant Systems. These results demonstrate that T-cell screening of the Mtb genome can be used to identify CD4+ T-cell antigens that are candidates for vaccine development.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2008.10.056</identifier><identifier>PMID: 19000730</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Adjuvants ; Allergy and Immunology ; Amino Acid Sequence ; Animals ; Antigens ; Antigens, Bacterial - chemistry ; Antigens, Bacterial - genetics ; Antigens, Bacterial - immunology ; Applied microbiology ; Bacteriology ; Biological and medical sciences ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - microbiology ; Cell Line ; Cloning ; Cloning, Molecular - methods ; E coli ; Epitope Mapping ; Escherichia coli ; Escherichia coli - genetics ; Escherichia coli - metabolism ; Filtrate ; Fundamental and applied biological sciences. Psychology ; Glycerol ; Guinea Pigs ; Humans ; Immunization ; Infections ; Lymphocyte Activation ; Mice ; Microbiology ; Miscellaneous ; Molecular Sequence Data ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Proteins ; Sequence Alignment ; Skin ; T lymphocytes ; Tuberculosis ; Tuberculosis - immunology ; Tuberculosis - microbiology ; Tuberculosis - prevention & control ; Tuberculosis Vaccines - administration & dosage ; Tuberculosis Vaccines - genetics ; Tuberculosis Vaccines - immunology ; Vaccination ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><ispartof>Vaccine, 2009-01, Vol.27 (2), p.223-233</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><rights>Copyright Elsevier Limited Jan 7, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c661t-e9e385b3ef7808d72e230cf625beb88b4134fcf1d60e152298b67709f016a56e3</citedby><cites>FETCH-LOGICAL-c661t-e9e385b3ef7808d72e230cf625beb88b4134fcf1d60e152298b67709f016a56e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1490551725?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,64361,64363,64365,65309,72215</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21039638$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19000730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Coler, Rhea N</creatorcontrib><creatorcontrib>Dillon, Davin C</creatorcontrib><creatorcontrib>Skeiky, Yasir A.W</creatorcontrib><creatorcontrib>Kahn, Maria</creatorcontrib><creatorcontrib>Orme, Ian M</creatorcontrib><creatorcontrib>Lobet, Yves</creatorcontrib><creatorcontrib>Reed, Steven G</creatorcontrib><creatorcontrib>Alderson, Mark R</creatorcontrib><title>Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract To identify Mycobacterium tuberculosis (Mtb) antigens as candidates for a subunit vaccine against tuberculosis (TB), we have employed a CD4+ T-cell expression screening method. Mtb-specific CD4+ T-cell lines from nine healthy PPD positive donors were stimulated with different antigenic substrates including autologous dendritic cells (DC) infected with Mtb, or cultured with culture filtrate proteins (CFP), and purified protein derivative of Mtb (PPD). These lines were used to screen a genomic Mtb library expressed in Escherichia coli and processed and presented by autologous DC. This screening led to the recovery of numerous T-cell antigens, including both novel and previously described antigens. One of these novel antigens, referred to as Mtb9.8 (Rv0287), was recognized by multiple T-cell lines, stimulated with either Mtb-infected DC or CFP. Using the mouse and guinea pig models of TB, high levels of IFN-γ were produced, and solid protection from Mtb challenge was observed following immunization with Mtb9.8 formulated in either AS02A or AS01B Adjuvant Systems. These results demonstrate that T-cell screening of the Mtb genome can be used to identify CD4+ T-cell antigens that are candidates for vaccine development.</description><subject>Adjuvants</subject><subject>Allergy and Immunology</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antigens</subject><subject>Antigens, Bacterial - chemistry</subject><subject>Antigens, Bacterial - genetics</subject><subject>Antigens, Bacterial - immunology</subject><subject>Applied microbiology</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - microbiology</subject><subject>Cell Line</subject><subject>Cloning</subject><subject>Cloning, Molecular - methods</subject><subject>E coli</subject><subject>Epitope Mapping</subject><subject>Escherichia coli</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - metabolism</subject><subject>Filtrate</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glycerol</subject><subject>Guinea Pigs</subject><subject>Humans</subject><subject>Immunization</subject><subject>Infections</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Molecular Sequence Data</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Proteins</subject><subject>Sequence Alignment</subject><subject>Skin</subject><subject>T lymphocytes</subject><subject>Tuberculosis</subject><subject>Tuberculosis - immunology</subject><subject>Tuberculosis - microbiology</subject><subject>Tuberculosis - prevention & control</subject><subject>Tuberculosis Vaccines - administration & dosage</subject><subject>Tuberculosis Vaccines - genetics</subject><subject>Tuberculosis Vaccines - immunology</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkk1v1DAQhiMEotvCTwBFQvSCsozt2HEuRWj5qlTEgSJxsxxn0nqbtRc7WbH_HoeNWuilJ1vjZ17PzDtZ9oLAkgARb9fLnTbGOlxSAJliS-DiUbYgsmIF5UQ-zhZARVmUBH4eZccxrgGAM1I_zY5Ine4Vg0V2c96iG2xnjR6sd7nv8q974xttBgx23OTD2GAwY--jjfn8ZW60a22rB4z5GK27yq_HjXb56kP5Jr8sDPZ9zPH3NmCMk6jpvUvUs-xJp_uIz-fzJPvx6ePl6ktx8e3z-er9RWGEIEOBNTLJG4ZdJUG2FUXKwHSC8gYbKZuSsLIzHWkFIOGU1rIRVQV1l8aiuUB2kp0ddLdjs8HWpAaD7tU22I0Oe-W1Vf-_OHutrvxOUVExCZAETmeB4H-NGAe1sXHqSjv0Y1QicaKW7EGQAqs5oTyBr-6Baz8Gl6agSFkD56T6S_EDZYKPMWB3WzMBNbmu1mq2QE2uT-Hkesp7-W_Dd1mzzQl4PQM6Gt13QTtj4y1HSapTMJm4dwcOkz07i0FFY9EZbG1AM6jW2wdLObunYHrr0nb1N7jHeNe1ilSB-j6t6LShIIGUZcXYH4sc47Y</recordid><startdate>20090107</startdate><enddate>20090107</enddate><creator>Coler, Rhea N</creator><creator>Dillon, Davin C</creator><creator>Skeiky, Yasir A.W</creator><creator>Kahn, Maria</creator><creator>Orme, Ian M</creator><creator>Lobet, Yves</creator><creator>Reed, Steven G</creator><creator>Alderson, Mark R</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090107</creationdate><title>Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning</title><author>Coler, Rhea N ; Dillon, Davin C ; Skeiky, Yasir A.W ; Kahn, Maria ; Orme, Ian M ; Lobet, Yves ; Reed, Steven G ; Alderson, Mark R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c661t-e9e385b3ef7808d72e230cf625beb88b4134fcf1d60e152298b67709f016a56e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adjuvants</topic><topic>Allergy and Immunology</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antigens</topic><topic>Antigens, Bacterial - chemistry</topic><topic>Antigens, Bacterial - genetics</topic><topic>Antigens, Bacterial - immunology</topic><topic>Applied microbiology</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD4-Positive T-Lymphocytes - microbiology</topic><topic>Cell Line</topic><topic>Cloning</topic><topic>Cloning, Molecular - methods</topic><topic>E coli</topic><topic>Epitope Mapping</topic><topic>Escherichia coli</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - metabolism</topic><topic>Filtrate</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glycerol</topic><topic>Guinea Pigs</topic><topic>Humans</topic><topic>Immunization</topic><topic>Infections</topic><topic>Lymphocyte Activation</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Molecular Sequence Data</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - immunology</topic><topic>Proteins</topic><topic>Sequence Alignment</topic><topic>Skin</topic><topic>T lymphocytes</topic><topic>Tuberculosis</topic><topic>Tuberculosis - immunology</topic><topic>Tuberculosis - microbiology</topic><topic>Tuberculosis - prevention & control</topic><topic>Tuberculosis Vaccines - administration & dosage</topic><topic>Tuberculosis Vaccines - genetics</topic><topic>Tuberculosis Vaccines - immunology</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coler, Rhea N</creatorcontrib><creatorcontrib>Dillon, Davin C</creatorcontrib><creatorcontrib>Skeiky, Yasir A.W</creatorcontrib><creatorcontrib>Kahn, Maria</creatorcontrib><creatorcontrib>Orme, Ian M</creatorcontrib><creatorcontrib>Lobet, Yves</creatorcontrib><creatorcontrib>Reed, Steven G</creatorcontrib><creatorcontrib>Alderson, Mark R</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coler, Rhea N</au><au>Dillon, Davin C</au><au>Skeiky, Yasir A.W</au><au>Kahn, Maria</au><au>Orme, Ian M</au><au>Lobet, Yves</au><au>Reed, Steven G</au><au>Alderson, Mark R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2009-01-07</date><risdate>2009</risdate><volume>27</volume><issue>2</issue><spage>223</spage><epage>233</epage><pages>223-233</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><coden>VACCDE</coden><abstract>Abstract To identify Mycobacterium tuberculosis (Mtb) antigens as candidates for a subunit vaccine against tuberculosis (TB), we have employed a CD4+ T-cell expression screening method. Mtb-specific CD4+ T-cell lines from nine healthy PPD positive donors were stimulated with different antigenic substrates including autologous dendritic cells (DC) infected with Mtb, or cultured with culture filtrate proteins (CFP), and purified protein derivative of Mtb (PPD). These lines were used to screen a genomic Mtb library expressed in Escherichia coli and processed and presented by autologous DC. This screening led to the recovery of numerous T-cell antigens, including both novel and previously described antigens. One of these novel antigens, referred to as Mtb9.8 (Rv0287), was recognized by multiple T-cell lines, stimulated with either Mtb-infected DC or CFP. Using the mouse and guinea pig models of TB, high levels of IFN-γ were produced, and solid protection from Mtb challenge was observed following immunization with Mtb9.8 formulated in either AS02A or AS01B Adjuvant Systems. These results demonstrate that T-cell screening of the Mtb genome can be used to identify CD4+ T-cell antigens that are candidates for vaccine development.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>19000730</pmid><doi>10.1016/j.vaccine.2008.10.056</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adjuvants Allergy and Immunology Amino Acid Sequence Animals Antigens Antigens, Bacterial - chemistry Antigens, Bacterial - genetics Antigens, Bacterial - immunology Applied microbiology Bacteriology Biological and medical sciences CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - microbiology Cell Line Cloning Cloning, Molecular - methods E coli Epitope Mapping Escherichia coli Escherichia coli - genetics Escherichia coli - metabolism Filtrate Fundamental and applied biological sciences. Psychology Glycerol Guinea Pigs Humans Immunization Infections Lymphocyte Activation Mice Microbiology Miscellaneous Molecular Sequence Data Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Proteins Sequence Alignment Skin T lymphocytes Tuberculosis Tuberculosis - immunology Tuberculosis - microbiology Tuberculosis - prevention & control Tuberculosis Vaccines - administration & dosage Tuberculosis Vaccines - genetics Tuberculosis Vaccines - immunology Vaccination Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) |
title | Identification of Mycobacterium tuberculosis vaccine candidates using human CD4+ T-cells expression cloning |
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