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Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination

Identifieur interne : 000067 ( PascalFrancis/Checkpoint ); précédent : 000066; suivant : 000068

Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination

Auteurs : Wing-Pui Kong [États-Unis] ; LAN WU [États-Unis] ; Timothy C. Wallstrom [États-Unis] ; Will Fischer [États-Unis] ; Zhi-Yong Yang [États-Unis] ; Sung-Youl Ko [États-Unis] ; Norman L. Letvin [États-Unis] ; Barton F. Haynes [États-Unis] ; Beatrice H. Hahn [États-Unis] ; Bette Korber [États-Unis] ; Gary J. Nabel [États-Unis]

Source :

RBID : Pascal:09-0131147

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English descriptors

Abstract

An effective AIDS vaccine must control highly diverse circulating strains of human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV-1 Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential T-cell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. One-, two-, and three-mosaic sets that increased theoretical epitope coverage were developed. The breadth and magnitude of T-cell immunity stimulated by these vaccines were compared to those for natural strain Envs; additional comparisons were performed on mutant Envs, including gp160 or gp145 with or without V regions and gp41 deletions. Among them, the two- or three-mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the three-mosaic set elicited responses to an average of eight peptide pools, compared to two pools for a set of three natural Envs. Synthetic mosaic HIV-1 antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T-cell-based HIV-1 vaccines.


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Pascal:09-0131147

Le document en format XML

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<div type="abstract" xml:lang="en">An effective AIDS vaccine must control highly diverse circulating strains of human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV-1 Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential T-cell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. One-, two-, and three-mosaic sets that increased theoretical epitope coverage were developed. The breadth and magnitude of T-cell immunity stimulated by these vaccines were compared to those for natural strain Envs; additional comparisons were performed on mutant Envs, including gp160 or gp145 with or without V regions and gp41 deletions. Among them, the two- or three-mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the three-mosaic set elicited responses to an average of eight peptide pools, compared to two pools for a set of three natural Envs. Synthetic mosaic HIV-1 antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T-cell-based HIV-1 vaccines.</div>
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<s1>Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive</s1>
<s2>Bethesda, Maryland 20892-3005</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="02">
<s1>Los Alamos National Laboratory, MS K710, T-10</s1>
<s2>Los Alamos, New Mexico 87545</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="03">
<s1>Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, P.O. Box 15732</s1>
<s2>Boston, Massachusetts 021153</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="04">
<s1>Duke Human Vaccine Institute, Duke University Medical Center, MSRBII Building Room 4085, P.O. Box 103020, Research Drive</s1>
<s2>Durham, North Carolina 27710</s2>
<s3>USA</s3>
<sZ>8 aut.</sZ>
</fA14>
<fA14 i1="05">
<s1>Department of Medicine, University of Alabama at Birmingham, Kaul 816, 720 20th Street South</s1>
<s2>Birmingham, Alabama 35294</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="06">
<s1>Santa Fe Institute, 1399 Hyde Park Road</s1>
<s2>Santa Fe, New Mexico 87501</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
</fA14>
<fA20>
<s1>2201-2215</s1>
</fA20>
<fA21>
<s1>2009</s1>
</fA21>
<fA23 i1="01">
<s0>ENG</s0>
</fA23>
<fA43 i1="01">
<s1>INIST</s1>
<s2>13592</s2>
<s5>354000187296090140</s5>
</fA43>
<fA44>
<s0>0000</s0>
<s1>© 2009 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45>
<s0>58 ref.</s0>
</fA45>
<fA47 i1="01" i2="1">
<s0>09-0131147</s0>
</fA47>
<fA60>
<s1>P</s1>
</fA60>
<fA61>
<s0>A</s0>
</fA61>
<fA64 i1="01" i2="1">
<s0>Journal of virology</s0>
</fA64>
<fA66 i1="01">
<s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG">
<s0>An effective AIDS vaccine must control highly diverse circulating strains of human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV-1 Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential T-cell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. One-, two-, and three-mosaic sets that increased theoretical epitope coverage were developed. The breadth and magnitude of T-cell immunity stimulated by these vaccines were compared to those for natural strain Envs; additional comparisons were performed on mutant Envs, including gp160 or gp145 with or without V regions and gp41 deletions. Among them, the two- or three-mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the three-mosaic set elicited responses to an average of eight peptide pools, compared to two pools for a set of three natural Envs. Synthetic mosaic HIV-1 antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T-cell-based HIV-1 vaccines.</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002A05C10</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Virus HIV1</s0>
<s2>NW</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>HIV-1 virus</s0>
<s2>NW</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>HIV-1 virus</s0>
<s2>NW</s2>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Immunité cellulaire</s0>
<s5>05</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>Cellular immunity</s0>
<s5>05</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Inmunidad celular</s0>
<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Vaccin génétique</s0>
<s5>06</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Genetic vaccine</s0>
<s5>06</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Vacuna genética</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Virologie</s0>
<s5>07</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Virology</s0>
<s5>07</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Virología</s0>
<s5>07</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>SIDA</s0>
<s5>14</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>AIDS</s0>
<s5>14</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>SIDA</s0>
<s5>14</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Virus immunodéficience humaine</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Human immunodeficiency virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Human immunodeficiency virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Lentivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Lentivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Lentivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Retroviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Retroviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Retroviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Immunodéficit</s0>
<s5>13</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Immune deficiency</s0>
<s5>13</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Inmunodeficiencia</s0>
<s5>13</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Virose</s0>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Viral disease</s0>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Virosis</s0>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Infection</s0>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Infection</s0>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Infección</s0>
</fC07>
<fC07 i1="08" i2="X" l="FRE">
<s0>Immunopathologie</s0>
<s5>17</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG">
<s0>Immunopathology</s0>
<s5>17</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA">
<s0>Inmunopatología</s0>
<s5>17</s5>
</fC07>
<fN21>
<s1>089</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
</list>
<tree>
<country name="États-Unis">
<noRegion>
<name sortKey="Kong, Wing Pui" sort="Kong, Wing Pui" uniqKey="Kong W" first="Wing-Pui" last="Kong">Wing-Pui Kong</name>
</noRegion>
<name sortKey="Fischer, Will" sort="Fischer, Will" uniqKey="Fischer W" first="Will" last="Fischer">Will Fischer</name>
<name sortKey="Hahn, Beatrice H" sort="Hahn, Beatrice H" uniqKey="Hahn B" first="Beatrice H." last="Hahn">Beatrice H. Hahn</name>
<name sortKey="Haynes, Barton F" sort="Haynes, Barton F" uniqKey="Haynes B" first="Barton F." last="Haynes">Barton F. Haynes</name>
<name sortKey="Ko, Sung Youl" sort="Ko, Sung Youl" uniqKey="Ko S" first="Sung-Youl" last="Ko">Sung-Youl Ko</name>
<name sortKey="Korber, Bette" sort="Korber, Bette" uniqKey="Korber B" first="Bette" last="Korber">Bette Korber</name>
<name sortKey="Korber, Bette" sort="Korber, Bette" uniqKey="Korber B" first="Bette" last="Korber">Bette Korber</name>
<name sortKey="Lan Wu" sort="Lan Wu" uniqKey="Lan Wu" last="Lan Wu">LAN WU</name>
<name sortKey="Letvin, Norman L" sort="Letvin, Norman L" uniqKey="Letvin N" first="Norman L." last="Letvin">Norman L. Letvin</name>
<name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J." last="Nabel">Gary J. Nabel</name>
<name sortKey="Wallstrom, Timothy C" sort="Wallstrom, Timothy C" uniqKey="Wallstrom T" first="Timothy C." last="Wallstrom">Timothy C. Wallstrom</name>
<name sortKey="Yang, Zhi Yong" sort="Yang, Zhi Yong" uniqKey="Yang Z" first="Zhi-Yong" last="Yang">Zhi-Yong Yang</name>
</country>
</tree>
</affiliations>
</record>

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