SIV DNA vaccine co‐administered with IL‐12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques
Identifieur interne : 001320 ( Istex/Corpus ); précédent : 001319; suivant : 001321SIV DNA vaccine co‐administered with IL‐12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques
Auteurs : Jean D. Boyer ; Tara M. Robinson ; Michele A. Kutzler ; R. Parkinson ; Sandra A. Calarota ; Maninder K. Sidhu ; Karuppiah Muthumani ; Mark Lewis ; George Pavlakis ; Barbara Felber ; David WeinerSource :
- Journal of Medical Primatology [ 0047-2565 ] ; 2005-10.
Abstract
Abstract: Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV‐1)‐specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co‐delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)‐12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL‐12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL‐12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co‐injected with the IL‐12 molecular adjuvant. The IL‐12 expanded antigen‐specific IFN‐γ positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component. The adjuvanted DNA vaccines illustrate that IL‐12 enhances a CD8 vaccine immune response, however, different cellular profiles.
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DOI: 10.1111/j.1600-0684.2005.00124.x
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Boyer</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Robinson, Tara M" sort="Robinson, Tara M" uniqKey="Robinson T" first="Tara M." last="Robinson">Tara M. Robinson</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Kutzler, Michele A" sort="Kutzler, Michele A" uniqKey="Kutzler M" first="Michele A." last="Kutzler">Michele A. Kutzler</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Parkinson, R" sort="Parkinson, R" uniqKey="Parkinson R" first="R." last="Parkinson">R. Parkinson</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Calarota, Sandra A" sort="Calarota, Sandra A" uniqKey="Calarota S" first="Sandra A." last="Calarota">Sandra A. Calarota</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Sidhu, Maninder K" sort="Sidhu, Maninder K" uniqKey="Sidhu M" first="Maninder K." last="Sidhu">Maninder K. 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The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co‐delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)‐12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL‐12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL‐12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co‐injected with the IL‐12 molecular adjuvant. The IL‐12 expanded antigen‐specific IFN‐γ positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component. The adjuvanted DNA vaccines illustrate that IL‐12 enhances a CD8 vaccine immune response, however, different cellular profiles.</abstract><qualityIndicators><score>9.388</score><pdfWordCount>5050</pdfWordCount><pdfCharCount>32320</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>9</pdfPageCount><pdfPageSize>595 x 782 pts</pdfPageSize><pdfWordsPerPage>561</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>true</refBibsNative><abstractWordCount>199</abstractWordCount><abstractCharCount>1294</abstractCharCount><keywordCount>5</keywordCount></qualityIndicators><title>SIV DNA vaccine co‐administered with IL‐12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques</title><pmid><json:string>16128921</json:string></pmid><genre><json:string>article</json:string></genre><host><title>Journal of Medical Primatology</title><language><json:string>unknown</json:string></language><doi><json:string>10.1111/(ISSN)1600-0684</json:string></doi><issn><json:string>0047-2565</json:string></issn><eissn><json:string>1600-0684</json:string></eissn><publisherId><json:string>JMP</json:string></publisherId><volume>34</volume><issue>5‐6</issue><pages><first>262</first><last>270</last><total>9</total></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2005</json:string></date><geogName></geogName><orgName><json:string>Cellular Technologies</json:string><json:string>Southern Research Institute</json:string><json:string>National Cancer Institute, Bethesda, MD, USA Background More</json:string><json:string>Cellular Technologies Limited, Cleveland</json:string><json:string>D Systems, Minneapolis</json:string><json:string>University of Pennsylvania School of Medicine</json:string><json:string>Department of Pathology and Laboratory</json:string><json:string>Emory University</json:string><json:string>Cell Sciences</json:string><json:string>Mabtech</json:string><json:string>American Association for the Accreditation of Laboratory Animal Care International and meet National Institute</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>F. 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vaccine co‐administered with IL‐12</title><author xml:id="author-0000"><persName><forename type="first">Jean D.</forename><surname>Boyer</surname></persName><affiliation><orgName type="laboratory">Department of Pathology and Laboratory Medicine</orgName><orgName type="institution">University of Pennsylvania School of Medicine</orgName><address><addrLine>Philadelphia</addrLine><addrLine>PA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">Tara M.</forename><surname>Robinson</surname></persName><affiliation><orgName type="laboratory">Department of Pathology and Laboratory Medicine</orgName><orgName type="institution">University of Pennsylvania School of Medicine</orgName><address><addrLine>Philadelphia</addrLine><addrLine>PA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">Michele A.</forename><surname>Kutzler</surname></persName><affiliation><orgName type="laboratory">Department of Pathology and Laboratory Medicine</orgName><orgName type="institution">University of Pennsylvania School of Medicine</orgName><address><addrLine>Philadelphia</addrLine><addrLine>PA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">R.</forename><surname>Parkinson</surname></persName><affiliation><orgName type="laboratory">Department of Pathology and Laboratory Medicine</orgName><orgName type="institution">University of Pennsylvania School of Medicine</orgName><address><addrLine>Philadelphia</addrLine><addrLine>PA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">Sandra A.</forename><surname>Calarota</surname></persName><affiliation><orgName type="laboratory">Department of Pathology and Laboratory Medicine</orgName><orgName type="institution">University of Pennsylvania School of Medicine</orgName><address><addrLine>Philadelphia</addrLine><addrLine>PA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0005"><persName><forename type="first">Maninder K.</forename><surname>Sidhu</surname></persName><affiliation><address><addrLine>Vaccine Discovery</addrLine><addrLine>Wyeth, Pearl River, NY</addrLine></address></affiliation></author><author xml:id="author-0006"><persName><forename type="first">Karuppiah</forename><surname>Muthumani</surname></persName><affiliation><orgName type="laboratory">Department of Pathology and Laboratory Medicine</orgName><orgName type="institution">University of Pennsylvania School of Medicine</orgName><address><addrLine>Philadelphia</addrLine><addrLine>PA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0007"><persName><forename type="first">Mark</forename><surname>Lewis</surname></persName><affiliation><address><addrLine>Bioqual</addrLine><addrLine>Frederick, MD</addrLine></address></affiliation></author><author xml:id="author-0008"><persName><forename type="first">George</forename><surname>Pavlakis</surname></persName><affiliation><orgName type="institution">National Cancer Institute</orgName><address><addrLine>Bethesda</addrLine><addrLine>MD, USA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0009"><persName><forename type="first">Barbara</forename><surname>Felber</surname></persName><affiliation><orgName type="institution">National Cancer Institute</orgName><address><addrLine>Bethesda</addrLine><addrLine>MD, USA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0010"><persName><forename type="first">David</forename><surname>Weiner</surname></persName><affiliation><orgName type="laboratory">Department of Pathology and Laboratory Medicine</orgName><orgName type="institution">University of Pennsylvania School of Medicine</orgName><address><addrLine>Philadelphia</addrLine><addrLine>PA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><idno type="istex">2D6BC5129725C3A72C70E64BC34F10E345343B1F</idno><idno type="ark">ark:/67375/WNG-8X7H74N0-Q</idno><idno type="DOI">10.1111/j.1600-0684.2005.00124.x</idno><idno type="unit">JMP124</idno><idno type="toTypesetVersion">file:JMP.JMP124.pdf</idno></analytic><monogr><title level="j" type="main">Journal of Medical Primatology</title><title level="j" type="alt">JOURNAL OF MEDICAL PRIMATOLOGY</title><idno type="pISSN">0047-2565</idno><idno type="eISSN">1600-0684</idno><idno type="book-DOI">10.1111/(ISSN)1600-0684</idno><idno type="book-part-DOI">10.1111/jmp.2005.34.issue-5-6</idno><idno type="product">JMP</idno><idno type="publisherDivision">ST</idno><imprint><biblScope unit="vol">34</biblScope><biblScope unit="issue">5‐6</biblScope><biblScope unit="page" from="262">262</biblScope><biblScope unit="page" to="270">270</biblScope><biblScope unit="page-count">9</biblScope><publisher>Munksgaard International Publishers</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2005-10"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><encodingDesc><schemaRef type="ODD" url="https://xml-schema.delivery.istex.fr/tei-istex.odd"></schemaRef><appInfo><application ident="pub2tei" version="1.0.10" when="2019-12-20"><label>pub2TEI-ISTEX</label><desc>A set of style sheets for converting XML documents encoded in various scientific publisher formats into a common TEI format.
<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract xml:lang="en" style="main"><p><hi rend="bold">Abstract: </hi> Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV‐1)‐specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co‐delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)‐12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL‐12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL‐12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co‐injected with the IL‐12 molecular adjuvant. The IL‐12 expanded antigen‐specific IFN‐<hi rend="italic">γ</hi> positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component. The adjuvanted DNA vaccines illustrate that IL‐12 enhances a CD8 vaccine immune response, however, different cellular profiles.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="k1">vaccine</term><term xml:id="k2">DNA</term><term xml:id="k3">IL‐12</term><term xml:id="k4">HIV</term><term xml:id="k5">SIV</term></keywords><keywords rend="tocHeading1"><term>Original articles</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-8X7H74N0-Q/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Munksgaard International Publishers</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1600-0684</doi><issn type="print">0047-2565</issn><issn type="electronic">1600-0684</issn><idGroup><id type="product" value="JMP"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="JOURNAL OF MEDICAL PRIMATOLOGY">Journal of Medical Primatology</title></titleGroup></publicationMeta><publicationMeta level="part" position="10005"><doi origin="wiley">10.1111/jmp.2005.34.issue-5-6</doi><numberingGroup><numbering type="journalVolume" number="34">34</numbering><numbering type="journalIssue">5‐6</numbering></numberingGroup><coverDate startDate="2005-10">October 2005</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="6" status="forIssue"><doi origin="wiley">10.1111/j.1600-0684.2005.00124.x</doi><idGroup><id type="unit" value="JMP124"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="tocHeading1">Original articles</title></titleGroup><eventGroup><event type="firstOnline" date="2005-08-10"></event><event type="publishedOnlineFinalForm" date="2005-08-10"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.2 mode:FullText source:FullText result:FullText" date="2010-03-11"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-31"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-30"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="262">262</numbering><numbering type="pageLast" number="270">270</numbering></numberingGroup><correspondenceTo>David Weiner, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Tel.: +1 215 3498365; fax: +1 215 5733496;
e‐mail: <email>dbweiner@mail.med.upenn.edu</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:JMP.JMP124.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Accepted April 14, 2005.</unparsedEditorialHistory><countGroup><count type="figureTotal" number="4"></count><count type="tableTotal" number="1"></count></countGroup><titleGroup><title type="main">SIV DNA vaccine co‐administered with IL‐12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques</title><title type="shortAuthors"><b>Boyer et al.</b></title><title type="short"><b>SIV DNA vaccine co‐administered with IL‐12</b></title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>Jean D.</givenNames><familyName>Boyer</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>Tara M.</givenNames><familyName>Robinson</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>Michele A.</givenNames><familyName>Kutzler</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a1"><personName><givenNames>R.</givenNames><familyName>Parkinson</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a1"><personName><givenNames>Sandra A.</givenNames><familyName>Calarota</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a2"><personName><givenNames>Maninder K.</givenNames><familyName>Sidhu</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a1"><personName><givenNames>Karuppiah</givenNames><familyName>Muthumani</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a3"><personName><givenNames>Mark</givenNames><familyName>Lewis</familyName></personName></creator><creator creatorRole="author" xml:id="cr9" affiliationRef="#a4"><personName><givenNames>George</givenNames><familyName>Pavlakis</familyName></personName></creator><creator creatorRole="author" xml:id="cr10" affiliationRef="#a4"><personName><givenNames>Barbara</givenNames><familyName>Felber</familyName></personName></creator><creator creatorRole="author" xml:id="cr11" affiliationRef="#a1"><personName><givenNames>David</givenNames><familyName>Weiner</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="US"><unparsedAffiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</unparsedAffiliation></affiliation><affiliation xml:id="a2"><unparsedAffiliation>Vaccine Discovery, Wyeth, Pearl River, NY</unparsedAffiliation></affiliation><affiliation xml:id="a3"><unparsedAffiliation>Bioqual, Frederick, MD</unparsedAffiliation></affiliation><affiliation xml:id="a4" countryCode="US"><unparsedAffiliation>National Cancer Institute, Bethesda, MD, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">vaccine</keyword><keyword xml:id="k2">DNA</keyword><keyword xml:id="k3">IL‐12</keyword><keyword xml:id="k4">HIV</keyword><keyword xml:id="k5">SIV</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b>Abstract: </b> Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV‐1)‐specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co‐delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)‐12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL‐12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL‐12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co‐injected with the IL‐12 molecular adjuvant. The IL‐12 expanded antigen‐specific IFN‐<i>γ</i> positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component. The adjuvanted DNA vaccines illustrate that IL‐12 enhances a CD8 vaccine immune response, however, different cellular profiles.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1" numbered="no"><p>Funding: This was funded in part by NIH IPCP and HVDDT grants</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>SIV DNA vaccine co‐administered with IL‐12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>SIV DNA vaccine co‐administered with IL‐12</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>SIV DNA vaccine co‐administered with IL‐12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques</title></titleInfo><name type="personal"><namePart type="given">Jean D.</namePart><namePart type="family">Boyer</namePart><affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tara M.</namePart><namePart type="family">Robinson</namePart><affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michele A.</namePart><namePart type="family">Kutzler</namePart><affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Parkinson</namePart><affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sandra A.</namePart><namePart type="family">Calarota</namePart><affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maninder K.</namePart><namePart type="family">Sidhu</namePart><affiliation>Vaccine Discovery, Wyeth, Pearl River, NY</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karuppiah</namePart><namePart type="family">Muthumani</namePart><affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mark</namePart><namePart type="family">Lewis</namePart><affiliation>Bioqual, Frederick, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">George</namePart><namePart type="family">Pavlakis</namePart><affiliation>National Cancer Institute, Bethesda, MD, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Barbara</namePart><namePart type="family">Felber</namePart><affiliation>National Cancer Institute, Bethesda, MD, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="family">Weiner</namePart><affiliation>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Munksgaard International Publishers</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2005-10</dateIssued><edition>Accepted April 14, 2005.</edition><copyrightDate encoding="w3cdtf">2005</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">4</extent><extent unit="tables">1</extent></physicalDescription><abstract lang="en">Abstract: Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV‐1)‐specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co‐delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)‐12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL‐12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL‐12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co‐injected with the IL‐12 molecular adjuvant. The IL‐12 expanded antigen‐specific IFN‐γ positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component. The adjuvanted DNA vaccines illustrate that IL‐12 enhances a CD8 vaccine immune response, however, different cellular profiles.</abstract><subject lang="en"><genre>keywords</genre><topic>vaccine</topic><topic>DNA</topic><topic>IL‐12</topic><topic>HIV</topic><topic>SIV</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Medical Primatology</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">0047-2565</identifier><identifier type="eISSN">1600-0684</identifier><identifier type="DOI">10.1111/(ISSN)1600-0684</identifier><identifier type="PublisherID">JMP</identifier><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>34</number></detail><detail type="issue"><caption>no.</caption><number>5‐6</number></detail><extent unit="pages"><start>262</start><end>270</end><total>9</total></extent></part></relatedItem><relatedItem type="references" displayLabel="cit2"><titleInfo><title>The adjuvant effect of interleukin‐12 in a vaccine against Leishmania major</title></titleInfo><name type="personal"><namePart type="given">LC</namePart><namePart type="family">Afonso</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">TM</namePart><namePart type="family">Scharton</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">LQ</namePart><namePart type="family">Vieira</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Wysocka</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G</namePart><namePart type="family">Trinchieri</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P</namePart><namePart type="family">Scott</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Afonso LC, Scharton TM, Vieira, LQ, Wysocka M, Trinchieri G, Scott P: The adjuvant effect of interleukin‐12 in a vaccine against Leishmania major. 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