Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses
Identifieur interne : 001D64 ( Istex/Corpus ); précédent : 001D63; suivant : 001D65Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses
Auteurs : J. Gibson Lanier ; Mark J. Newman ; Eushin M. Lee ; Alessandro Sette ; Rafi AhmedSource :
- Vaccine [ 0264-410X ] ; 2000.
English descriptors
- Teeft :
- Adjuvant, Ahmed, Antibody responses, Assay, Block copolymers, Cell response, Cell responses, Choriomeningitis, Chronic infection, Clone, Copolymer, Cytotoxic, Elispot, Elispot assay, Emulsion, Epitope, Gibson lanier, Helper peptide, Immune responses, Immunization, Immunol, Lanier, Lcmv, Lymphocyte, Lymphocytic, Lymphocytic choriomeningitis virus, Lysis, Mice vaccinated, Mouse, Multiple emulsion, Naive mice, Nonionic, Nonionic block copolymers, Peptide, Peptide vaccination, Persistent infection, Pharmingen, Plaque assay, Secreting, Secreting cells, Spleen, Spleen cells, Splenocytes, Target cells, Vaccinated, Vaccinated mice, Vaccine, Viral, Viral challenge, Viral infection, Virol.
Abstract
Abstract: High molecular weight nonionic block copolymers have been developed as vaccine adjuvants. We employed these adjuvants in water-in-oil emulsion and multiple emulsion formulations with a synthetic peptide-based antigen vaccine to test their ability to prime anti-viral CD8+ T cell responses. Vaccines were made using the H-2d-restricted immunodominant peptide from lymphocytic choriomeningitis virus (LCMV), NP118–126, and administered to BALB/c ByJ (H-2d) mice. Peptide-containing emulsions were able to induce NP118–126 specific CTL and IFN-γ secreting CD8+ T cells in the vaccinated mice and these responses were maintained for at least 90 days post immunization. At all times, the responses induced by the copolymer formulations were equal to, or better than, formulations based on incomplete Freund's adjuvant (IFA). In addition, the responses induced by prophylactic vaccination using the multiple emulsion formulation resulted in accelerated viral clearance following infection with a strain of LCMV (clone 13) that causes a persistent infection in naı̈ve adult mice. These results indicate that peptide vaccination using a formulation based on high molecular weight nonionic block copolymer in a simple water-in-oil or a multiple emulsion format can induce virus-specific CD8+ T cell responses and confer protection sufficient enough to prevent the establishment of a persistent infection.
Url:
DOI: 10.1016/S0264-410X(99)00220-0
Links to Exploration step
ISTEX:059FA3AA7DDE80FF933E8FE39423728F1ACCFE72Le document en format XML
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Lee</name><affiliation><mods:affiliation>Vaxcel Inc., 154 Technology Parkway, Norcross, GA 30092, USA</mods:affiliation></affiliation></author><author><name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name><affiliation><mods:affiliation>Epimmune Inc., 6555 Nancy Ridge Rd., Suite 200, SanDiego, CA 92121, USA</mods:affiliation></affiliation></author><author><name sortKey="Ahmed, Rafi" sort="Ahmed, Rafi" uniqKey="Ahmed R" first="Rafi" last="Ahmed">Rafi Ahmed</name><affiliation><mods:affiliation>Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, 1510 Clifton Rd., Atlanta, GA 30322, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Tel: +1-404-727-3571; fax: +1-404-727-3722</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: ra@microbio.emory.edu</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:059FA3AA7DDE80FF933E8FE39423728F1ACCFE72</idno><date when="1999" year="1999">1999</date><idno type="doi">10.1016/S0264-410X(99)00220-0</idno><idno type="url">https://api.istex.fr/ark:/67375/6H6-X31TXSX2-6/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001D64</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001D64</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses</title><author><name sortKey="Gibson Lanier, J" sort="Gibson Lanier, J" uniqKey="Gibson Lanier J" first="J" last="Gibson Lanier">J. Gibson Lanier</name><affiliation><mods:affiliation>Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, 1510 Clifton Rd., Atlanta, GA 30322, USA</mods:affiliation></affiliation></author><author><name sortKey="Newman, Mark J" sort="Newman, Mark J" uniqKey="Newman M" first="Mark J" last="Newman">Mark J. Newman</name><affiliation><mods:affiliation>Vaxcel Inc., 154 Technology Parkway, Norcross, GA 30092, USA</mods:affiliation></affiliation></author><author><name sortKey="Lee, Eushin M" sort="Lee, Eushin M" uniqKey="Lee E" first="Eushin M" last="Lee">Eushin M. 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Tel: +1-404-727-3571; fax: +1-404-727-3722</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: ra@microbio.emory.edu</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Vaccine</title><title level="j" type="abbrev">JVAC</title><idno type="ISSN">0264-410X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000">2000</date><biblScope unit="volume">18</biblScope><biblScope unit="issue">5–6</biblScope><biblScope unit="page" from="549">549</biblScope><biblScope unit="page" to="557">557</biblScope></imprint><idno type="ISSN">0264-410X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Adjuvant</term><term>Ahmed</term><term>Antibody responses</term><term>Assay</term><term>Block copolymers</term><term>Cell response</term><term>Cell responses</term><term>Choriomeningitis</term><term>Chronic infection</term><term>Clone</term><term>Copolymer</term><term>Cytotoxic</term><term>Elispot</term><term>Elispot assay</term><term>Emulsion</term><term>Epitope</term><term>Gibson lanier</term><term>Helper peptide</term><term>Immune responses</term><term>Immunization</term><term>Immunol</term><term>Lanier</term><term>Lcmv</term><term>Lymphocyte</term><term>Lymphocytic</term><term>Lymphocytic choriomeningitis virus</term><term>Lysis</term><term>Mice vaccinated</term><term>Mouse</term><term>Multiple emulsion</term><term>Naive mice</term><term>Nonionic</term><term>Nonionic block copolymers</term><term>Peptide</term><term>Peptide vaccination</term><term>Persistent infection</term><term>Pharmingen</term><term>Plaque assay</term><term>Secreting</term><term>Secreting cells</term><term>Spleen</term><term>Spleen cells</term><term>Splenocytes</term><term>Target cells</term><term>Vaccinated</term><term>Vaccinated mice</term><term>Vaccine</term><term>Viral</term><term>Viral challenge</term><term>Viral infection</term><term>Virol</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: High molecular weight nonionic block copolymers have been developed as vaccine adjuvants. 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Tel: +1-404-727-3571; fax: +1-404-727-3722</json:string><json:string>E-mail: ra@microbio.emory.edu</json:string></affiliations></json:item></author><arkIstex>ark:/67375/6H6-X31TXSX2-6</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: High molecular weight nonionic block copolymers have been developed as vaccine adjuvants. We employed these adjuvants in water-in-oil emulsion and multiple emulsion formulations with a synthetic peptide-based antigen vaccine to test their ability to prime anti-viral CD8+ T cell responses. Vaccines were made using the H-2d-restricted immunodominant peptide from lymphocytic choriomeningitis virus (LCMV), NP118–126, and administered to BALB/c ByJ (H-2d) mice. Peptide-containing emulsions were able to induce NP118–126 specific CTL and IFN-γ secreting CD8+ T cells in the vaccinated mice and these responses were maintained for at least 90 days post immunization. At all times, the responses induced by the copolymer formulations were equal to, or better than, formulations based on incomplete Freund's adjuvant (IFA). In addition, the responses induced by prophylactic vaccination using the multiple emulsion formulation resulted in accelerated viral clearance following infection with a strain of LCMV (clone 13) that causes a persistent infection in naı̈ve adult mice. These results indicate that peptide vaccination using a formulation based on high molecular weight nonionic block copolymer in a simple water-in-oil or a multiple emulsion format can induce virus-specific CD8+ T cell responses and confer protection sufficient enough to prevent the establishment of a persistent infection.</abstract><qualityIndicators><score>9.376</score><pdfWordCount>5003</pdfWordCount><pdfCharCount>30685</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>9</pdfPageCount><pdfPageSize>595 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>198</abstractWordCount><abstractCharCount>1405</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses</title><pmid><json:string>10519946</json:string></pmid><pii><json:string>S0264-410X(99)00220-0</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Vaccine</title><language><json:string>unknown</json:string></language><publicationDate>2000</publicationDate><issn><json:string>0264-410X</json:string></issn><pii><json:string>S0264-410X(00)X0089-8</json:string></pii><volume>18</volume><issue>5–6</issue><pages><first>549</first><last>557</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1999</json:string></date><geogName></geogName><orgName><json:string>Vaxcel Inc.</json:string><json:string>Elsevier Science Ltd.</json:string><json:string>Emory University</json:string><json:string>Georgia Research Alliance TDI97</json:string></orgName><orgName_funder><json:string>Georgia Research Alliance TDI97</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Nancy Ridge</json:string><json:string>Jason K. Whitmire</json:string><json:string>Kaja Murali-Krishna</json:string><json:string>J. Gibson</json:string><json:string>Allan J. Zajac</json:string><json:string>Kaja</json:string><json:string>R. Ahmed</json:string><json:string>Morry Hsu</json:string><json:string>Jackson Laboratory</json:string><json:string>Jason Grayson</json:string><json:string>M. Suresh</json:string><json:string>La Jolla</json:string></persName><placeName><json:string>Bedford</json:string><json:string>GA</json:string><json:string>MA</json:string><json:string>Cambridge</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>[43,44]</json:string><json:string>[11,36]</json:string><json:string>[26,27]</json:string><json:string>[6]</json:string><json:string>Lanier et al.</json:string><json:string>Rollins Research Center, 1510</json:string><json:string>[11]</json:string><json:string>[8]</json:string><json:string>[1]</json:string><json:string>[32]</json:string><json:string>[3]</json:string><json:string>[10,42]</json:string><json:string>[37]</json:string><json:string>[6,7]</json:string><json:string>Epimmune Inc., 6555</json:string><json:string>[6,40,41]</json:string><json:string>[25]</json:string><json:string>[21,38,39]</json:string><json:string>[9]</json:string><json:string>[40]</json:string><json:string>[2]</json:string><json:string>[4,5]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-X31TXSX2-6</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - medicine, research & experimental</json:string><json:string>2 - immunology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - virology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Infectious Diseases</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Public Health, Environmental and Occupational Health</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Veterinary</json:string><json:string>3 - General Veterinary</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - General Immunology and Microbiology</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Molecular Medicine</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - chirurgie (generalites). transplantations, greffes d'organes et de tissus. pathologie des greffons</json:string></inist></categories><publicationDate>2000</publicationDate><copyrightDate>1999</copyrightDate><doi><json:string>10.1016/S0264-410X(99)00220-0</json:string></doi><id>059FA3AA7DDE80FF933E8FE39423728F1ACCFE72</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-X31TXSX2-6/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-X31TXSX2-6/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-X31TXSX2-6/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©1999 Elsevier Science Ltd</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</p></availability><date>1999</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Fig. 1: Induction of virus-specific CD8 cytotoxic T cell responses. Spleens were harvested from mice 8 d after immunization and CTL assay was performed following 6 d, in vitro stimulation with NP118–126 peptide (1 μg/ml). Cells were harvested and added to 51Cr-labeled target cells at the indicated Effector:Target (E:T) ratio. BALB/Cl7 target cells were either infected (closed circles) with Clone-13 24 h prior to assay or uninfected (open circles). Effector cells were splenocytes from BALB/c ByJ mice immunized with (A) W/O/W CRL1005 emulsion+NP118–126+OVA323–336, (B) W/O CRL1005 emulsion+NP118–126+OVA323–336, (C) IFA+NP118–126+OVA323–336, or (D) NP118–126+OVA323–336 alone. Data presented are averaged values from 3 experiments (n=7). Bars represent standard error of the mean.</note><note type="content">Fig. 2: Spleen cells from LCMV-immune (>60 d post-infection with LCMV Armstrong) or naive BALB/c mice were incubated with or without peptide NP118–126 for 5 h, followed by staining for surface CD8 and intracellular IFN-γ. The numbers shown indicate the percentage of CD8+ T cells that are positive for the IFN-γ stain.</note><note type="content">Fig. 3: Peptide-specific IFN-γ secreting cells result from peptide immunizations. Mice were immunized and 8 d later spleens were removed. The number of IFN-γ secreting cells was determined by IFN-γ ELISPOT assay. Values indicated represent averaged values from 3 experiments (n=5). Bars represent standard error of the mean. Limit of detection is indicated by a dashed line.</note><note type="content">Fig. 4: Longevity of enhanced T cell responses. (A) Secondary CTL responses from splenocytes of BALB/c ByJ mice immunized 8, 30 and 90 d prior to assay. CTL targets were BALB clone 7 cells (H-2d targets), either uncoated (open circles) or coated with 0.1μg/ml peptide (closed circles). (B) IFN-γ ELISPOT assay from splenocytes from BALB/c ByJ mice immunized 8, 30 and 90 d prior to assay. Diamonds indicate the number of LCMV-specific IFN-γ secreting cells per spleen for each individual mouse for each adjuvant group at the indicated assay time. Limit of detection is indicated by a dashed line.</note><note type="content">Fig. 5: Vaccination with NP118–126 plus copolymer in a multiple emulsion provides protection against challenge with a strain of LCMV that causes a chronic infection in naive adult mice. Thirty days following s.c. immunization of the peptide or peptide:adjuvant emulsion, mice were challenged with 2×106 pfu clone-13 i.v. Viral titers in the serum at 8 d post challenge were determined by plaque assay on Vero cells and the values for each individual mouse are indicated by a diamond. The detection limit is 50 pfu/ml indicated by a dashed line.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses</title><author xml:id="author-0000"><persName><forename type="first">J</forename><surname>Gibson Lanier</surname></persName><affiliation>Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, 1510 Clifton Rd., Atlanta, GA 30322, USA</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Mark J</forename><surname>Newman</surname></persName><affiliation>Vaxcel Inc., 154 Technology Parkway, Norcross, GA 30092, USA</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Eushin M</forename><surname>Lee</surname></persName><affiliation>Vaxcel Inc., 154 Technology Parkway, Norcross, GA 30092, USA</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Alessandro</forename><surname>Sette</surname></persName><affiliation>Epimmune Inc., 6555 Nancy Ridge Rd., Suite 200, SanDiego, CA 92121, USA</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Rafi</forename><surname>Ahmed</surname></persName><email>ra@microbio.emory.edu</email><affiliation>Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, 1510 Clifton Rd., Atlanta, GA 30322, USA</affiliation><affiliation>Corresponding author. Tel: +1-404-727-3571; fax: +1-404-727-3722</affiliation></author><idno type="istex">059FA3AA7DDE80FF933E8FE39423728F1ACCFE72</idno><idno type="ark">ark:/67375/6H6-X31TXSX2-6</idno><idno type="DOI">10.1016/S0264-410X(99)00220-0</idno><idno type="PII">S0264-410X(99)00220-0</idno></analytic><monogr><title level="j">Vaccine</title><title level="j" type="abbrev">JVAC</title><idno type="pISSN">0264-410X</idno><idno type="PII">S0264-410X(00)X0089-8</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000"></date><biblScope unit="volume">18</biblScope><biblScope unit="issue">5–6</biblScope><biblScope unit="page" from="549">549</biblScope><biblScope unit="page" to="557">557</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: High molecular weight nonionic block copolymers have been developed as vaccine adjuvants. We employed these adjuvants in water-in-oil emulsion and multiple emulsion formulations with a synthetic peptide-based antigen vaccine to test their ability to prime anti-viral CD8+ T cell responses. Vaccines were made using the H-2d-restricted immunodominant peptide from lymphocytic choriomeningitis virus (LCMV), NP118–126, and administered to BALB/c ByJ (H-2d) mice. Peptide-containing emulsions were able to induce NP118–126 specific CTL and IFN-γ secreting CD8+ T cells in the vaccinated mice and these responses were maintained for at least 90 days post immunization. At all times, the responses induced by the copolymer formulations were equal to, or better than, formulations based on incomplete Freund's adjuvant (IFA). In addition, the responses induced by prophylactic vaccination using the multiple emulsion formulation resulted in accelerated viral clearance following infection with a strain of LCMV (clone 13) that causes a persistent infection in naı̈ve adult mice. These results indicate that peptide vaccination using a formulation based on high molecular weight nonionic block copolymer in a simple water-in-oil or a multiple emulsion format can induce virus-specific CD8+ T cell responses and confer protection sufficient enough to prevent the establishment of a persistent infection.</p></abstract></profileDesc><revisionDesc><change when="2000">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-X31TXSX2-6/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr5" NDATA="IMAGE" name="gr5"></istex:entity><istex:entity SYSTEM="gr4a" NDATA="IMAGE" name="gr4a"></istex:entity><istex:entity SYSTEM="gr4b" NDATA="IMAGE" name="gr4b"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>JVAC</jid><aid>1663</aid><ce:pii>S0264-410X(99)00220-0</ce:pii><ce:doi>10.1016/S0264-410X(99)00220-0</ce:doi><ce:copyright type="full-transfer" year="1999">Elsevier Science Ltd</ce:copyright></item-info><head><ce:title>Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses</ce:title><ce:author-group><ce:author><ce:given-name>J</ce:given-name><ce:surname>Gibson Lanier</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Mark J</ce:given-name><ce:surname>Newman</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Eushin M</ce:given-name><ce:surname>Lee</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Alessandro</ce:given-name><ce:surname>Sette</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Rafi</ce:given-name><ce:surname>Ahmed</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref><ce:e-address>ra@microbio.emory.edu</ce:e-address></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, 1510 Clifton Rd., Atlanta, GA 30322, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Vaxcel Inc., 154 Technology Parkway, Norcross, GA 30092, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Epimmune Inc., 6555 Nancy Ridge Rd., Suite 200, SanDiego, CA 92121, USA</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel: +1-404-727-3571; fax: +1-404-727-3722</ce:text></ce:correspondence></ce:author-group><ce:date-received day="30" month="6" year="1998"></ce:date-received><ce:date-accepted day="19" month="4" year="1999"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>High molecular weight nonionic block copolymers have been developed as vaccine adjuvants. We employed these adjuvants in water-in-oil emulsion and multiple emulsion formulations with a synthetic peptide-based antigen vaccine to test their ability to prime anti-viral CD8<ce:sup>+</ce:sup> T cell responses. Vaccines were made using the H-2<ce:sup>d</ce:sup>-restricted immunodominant peptide from lymphocytic choriomeningitis virus (LCMV), NP118–126, and administered to BALB/c ByJ (H-2<ce:sup>d</ce:sup>) mice. Peptide-containing emulsions were able to induce NP118–126 specific CTL and IFN-γ secreting CD8<ce:sup>+</ce:sup> T cells in the vaccinated mice and these responses were maintained for at least 90 days post immunization. At all times, the responses induced by the copolymer formulations were equal to, or better than, formulations based on incomplete Freund's adjuvant (IFA). In addition, the responses induced by prophylactic vaccination using the multiple emulsion formulation resulted in accelerated viral clearance following infection with a strain of LCMV (clone 13) that causes a persistent infection in naı̈ve adult mice. These results indicate that peptide vaccination using a formulation based on high molecular weight nonionic block copolymer in a simple water-in-oil or a multiple emulsion format can induce virus-specific CD8<ce:sup>+</ce:sup> T cell responses and confer protection sufficient enough to prevent the establishment of a persistent infection.</ce:simple-para></ce:abstract-sec></ce:abstract></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses</title></titleInfo><name type="personal"><namePart type="given">J</namePart><namePart type="family">Gibson Lanier</namePart><affiliation>Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, 1510 Clifton Rd., Atlanta, GA 30322, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mark J</namePart><namePart type="family">Newman</namePart><affiliation>Vaxcel Inc., 154 Technology Parkway, Norcross, GA 30092, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eushin M</namePart><namePart type="family">Lee</namePart><affiliation>Vaxcel Inc., 154 Technology Parkway, Norcross, GA 30092, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alessandro</namePart><namePart type="family">Sette</namePart><affiliation>Epimmune Inc., 6555 Nancy Ridge Rd., Suite 200, SanDiego, CA 92121, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rafi</namePart><namePart type="family">Ahmed</namePart><affiliation>Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, 1510 Clifton Rd., Atlanta, GA 30322, USA</affiliation><affiliation>Corresponding author. Tel: +1-404-727-3571; fax: +1-404-727-3722</affiliation><affiliation>E-mail: ra@microbio.emory.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued><copyrightDate encoding="w3cdtf">1999</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: High molecular weight nonionic block copolymers have been developed as vaccine adjuvants. We employed these adjuvants in water-in-oil emulsion and multiple emulsion formulations with a synthetic peptide-based antigen vaccine to test their ability to prime anti-viral CD8+ T cell responses. Vaccines were made using the H-2d-restricted immunodominant peptide from lymphocytic choriomeningitis virus (LCMV), NP118–126, and administered to BALB/c ByJ (H-2d) mice. Peptide-containing emulsions were able to induce NP118–126 specific CTL and IFN-γ secreting CD8+ T cells in the vaccinated mice and these responses were maintained for at least 90 days post immunization. At all times, the responses induced by the copolymer formulations were equal to, or better than, formulations based on incomplete Freund's adjuvant (IFA). In addition, the responses induced by prophylactic vaccination using the multiple emulsion formulation resulted in accelerated viral clearance following infection with a strain of LCMV (clone 13) that causes a persistent infection in naı̈ve adult mice. These results indicate that peptide vaccination using a formulation based on high molecular weight nonionic block copolymer in a simple water-in-oil or a multiple emulsion format can induce virus-specific CD8+ T cell responses and confer protection sufficient enough to prevent the establishment of a persistent infection.</abstract><note type="content">Fig. 1: Induction of virus-specific CD8 cytotoxic T cell responses. Spleens were harvested from mice 8 d after immunization and CTL assay was performed following 6 d, in vitro stimulation with NP118–126 peptide (1 μg/ml). Cells were harvested and added to 51Cr-labeled target cells at the indicated Effector:Target (E:T) ratio. BALB/Cl7 target cells were either infected (closed circles) with Clone-13 24 h prior to assay or uninfected (open circles). Effector cells were splenocytes from BALB/c ByJ mice immunized with (A) W/O/W CRL1005 emulsion+NP118–126+OVA323–336, (B) W/O CRL1005 emulsion+NP118–126+OVA323–336, (C) IFA+NP118–126+OVA323–336, or (D) NP118–126+OVA323–336 alone. Data presented are averaged values from 3 experiments (n=7). Bars represent standard error of the mean.</note><note type="content">Fig. 2: Spleen cells from LCMV-immune (>60 d post-infection with LCMV Armstrong) or naive BALB/c mice were incubated with or without peptide NP118–126 for 5 h, followed by staining for surface CD8 and intracellular IFN-γ. The numbers shown indicate the percentage of CD8+ T cells that are positive for the IFN-γ stain.</note><note type="content">Fig. 3: Peptide-specific IFN-γ secreting cells result from peptide immunizations. Mice were immunized and 8 d later spleens were removed. The number of IFN-γ secreting cells was determined by IFN-γ ELISPOT assay. Values indicated represent averaged values from 3 experiments (n=5). Bars represent standard error of the mean. Limit of detection is indicated by a dashed line.</note><note type="content">Fig. 4: Longevity of enhanced T cell responses. (A) Secondary CTL responses from splenocytes of BALB/c ByJ mice immunized 8, 30 and 90 d prior to assay. CTL targets were BALB clone 7 cells (H-2d targets), either uncoated (open circles) or coated with 0.1μg/ml peptide (closed circles). (B) IFN-γ ELISPOT assay from splenocytes from BALB/c ByJ mice immunized 8, 30 and 90 d prior to assay. Diamonds indicate the number of LCMV-specific IFN-γ secreting cells per spleen for each individual mouse for each adjuvant group at the indicated assay time. Limit of detection is indicated by a dashed line.</note><note type="content">Fig. 5: Vaccination with NP118–126 plus copolymer in a multiple emulsion provides protection against challenge with a strain of LCMV that causes a chronic infection in naive adult mice. Thirty days following s.c. immunization of the peptide or peptide:adjuvant emulsion, mice were challenged with 2×106 pfu clone-13 i.v. Viral titers in the serum at 8 d post challenge were determined by plaque assay on Vero cells and the values for each individual mouse are indicated by a diamond. The detection limit is 50 pfu/ml indicated by a dashed line.</note><relatedItem type="host"><titleInfo><title>Vaccine</title></titleInfo><titleInfo type="abbreviated"><title>JVAC</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><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued></originInfo><identifier type="ISSN">0264-410X</identifier><identifier type="PII">S0264-410X(00)X0089-8</identifier><part><date>2000</date><detail type="volume"><number>18</number><caption>vol.</caption></detail><detail type="issue"><number>5–6</number><caption>no.</caption></detail><extent unit="issue-pages"><start>387</start><end>576</end></extent><extent unit="pages"><start>549</start><end>557</end></extent></part></relatedItem><identifier type="istex">059FA3AA7DDE80FF933E8FE39423728F1ACCFE72</identifier><identifier type="ark">ark:/67375/6H6-X31TXSX2-6</identifier><identifier type="DOI">10.1016/S0264-410X(99)00220-0</identifier><identifier type="PII">S0264-410X(99)00220-0</identifier><accessCondition type="use and reproduction" contentType="copyright">©1999 Elsevier Science Ltd</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Elsevier Science Ltd, ©1999</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-X31TXSX2-6/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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