Broad Immunogenicity of a Multigene, Multiclade HIV-1 DNA Vaccine Boosted with Heterologous HIV-1 Recombinant Modified Vaccinia Virus Ankara
Identifieur interne : 002A45 ( Main/Exploration ); précédent : 002A44; suivant : 002A46Broad Immunogenicity of a Multigene, Multiclade HIV-1 DNA Vaccine Boosted with Heterologous HIV-1 Recombinant Modified Vaccinia Virus Ankara
Auteurs : Eric Sandström [Suède] ; Charlotta Nilsson [Suède] ; Bo Hejdeman [Suède] ; Andreas Br Ve [Suède] ; Göran Bratt [Suède] ; Merlin Robb [États-Unis] ; Josephine Cox [États-Unis] ; Thomas Vancott [États-Unis] ; Mary Marovich [Suède] ; Richard Stout [États-Unis] ; Said Aboud [Tanzanie] ; Muhammad Bakari [Tanzanie] ; Kisali Pallangyo [Tanzanie] ; Karl Ljungberg [Suède] ; Bernard Moss [États-Unis] ; Patricia Earl [États-Unis] ; Nelson Michael [États-Unis] ; Deborah Birx [Suède] ; Fred Mhalu [Tanzanie] ; Britta Wahren [Suède] ; Gunnel Biberfeld [Suède]Source :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2008.
Abstract
Background. A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine. Methods. Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune responses were monitored with HIV-specific interferon (IFN)-γ and interleukin (IL)-2 ELISpot and lymphoproliferative assays (LPAs). Results. Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-γ responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-γ responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-γ production was detected in both the CD8+ T cell compartment (5 of 9 selected vaccinees) and the CD4+ T cell compartment (9 of 9). ELISpot results showed that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4 mg administered intramuscularly in priming for the MVA boosting vaccine. Conclusion. This HIV-DNA priming-MVA boosting approach is safe and highly immunogenic. Trials registration. International Standard Randomised Controlled Trial number: ISRCTN32604572.
Url:
DOI: 10.1086/592507
Affiliations:
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last="Nilsson">Charlotta Nilsson</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>the Swedish Institute for Infectious Disease Control, and Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Hejdeman, Bo" sort="Hejdeman, Bo" uniqKey="Hejdeman B" first="Bo" last="Hejdeman">Bo Hejdeman</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Br Ve, Andreas" sort="Br Ve, Andreas" uniqKey="Br Ve A" first="Andreas" last="Br Ve">Andreas Br Ve</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>the Swedish Institute for Infectious Disease Control, and Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Bratt, Goran" sort="Bratt, Goran" uniqKey="Bratt G" first="Göran" last="Bratt">Göran Bratt</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Robb, Merlin" sort="Robb, Merlin" uniqKey="Robb M" first="Merlin" last="Robb">Merlin Robb</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Walter Reed Army Institute for Research, Department of Retrovirology, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Cox, Josephine" sort="Cox, Josephine" uniqKey="Cox J" first="Josephine" last="Cox">Josephine Cox</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Walter Reed Army Institute for Research, Department of Retrovirology, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Vancott, Thomas" sort="Vancott, Thomas" uniqKey="Vancott T" first="Thomas" last="Vancott">Thomas Vancott</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Walter Reed Army Institute for Research, Department of Retrovirology, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Marovich, Mary" sort="Marovich, Mary" uniqKey="Marovich M" first="Mary" last="Marovich">Mary Marovich</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Stout, Richard" sort="Stout, Richard" uniqKey="Stout R" first="Richard" last="Stout">Richard Stout</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oregon</region></placeName><wicri:cityArea>Bioject, Portland</wicri:cityArea></affiliation></author><author><name sortKey="Aboud, Said" sort="Aboud, Said" uniqKey="Aboud S" first="Said" last="Aboud">Said Aboud</name><affiliation wicri:level="1"><country xml:lang="fr">Tanzanie</country><wicri:regionArea>Muhimbili University of Health and Allied Sciences, Dar es Salaam</wicri:regionArea><wicri:noRegion>Dar es Salaam</wicri:noRegion></affiliation></author><author><name sortKey="Bakari, Muhammad" sort="Bakari, Muhammad" uniqKey="Bakari M" first="Muhammad" last="Bakari">Muhammad Bakari</name><affiliation wicri:level="1"><country xml:lang="fr">Tanzanie</country><wicri:regionArea>Muhimbili University of Health and Allied Sciences, Dar es Salaam</wicri:regionArea><wicri:noRegion>Dar es Salaam</wicri:noRegion></affiliation></author><author><name sortKey="Pallangyo, Kisali" sort="Pallangyo, Kisali" uniqKey="Pallangyo K" first="Kisali" last="Pallangyo">Kisali Pallangyo</name><affiliation wicri:level="1"><country xml:lang="fr">Tanzanie</country><wicri:regionArea>Muhimbili University of Health and Allied Sciences, Dar es Salaam</wicri:regionArea><wicri:noRegion>Dar es Salaam</wicri:noRegion></affiliation></author><author><name sortKey="Ljungberg, Karl" sort="Ljungberg, Karl" uniqKey="Ljungberg K" first="Karl" last="Ljungberg">Karl Ljungberg</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Oncology-Pathology, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Moss, Bernard" sort="Moss, Bernard" uniqKey="Moss B" first="Bernard" last="Moss">Bernard Moss</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Earl, Patricia" sort="Earl, Patricia" uniqKey="Earl P" first="Patricia" last="Earl">Patricia Earl</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Michael, Nelson" sort="Michael, Nelson" uniqKey="Michael N" first="Nelson" last="Michael">Nelson Michael</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Walter Reed Army Institute for Research, Department of Retrovirology, Rockville</wicri:cityArea></affiliation></author><author><name sortKey="Birx, Deborah" sort="Birx, Deborah" uniqKey="Birx D" first="Deborah" last="Birx">Deborah Birx</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Mhalu, Fred" sort="Mhalu, Fred" uniqKey="Mhalu F" first="Fred" last="Mhalu">Fred Mhalu</name><affiliation wicri:level="1"><country xml:lang="fr">Tanzanie</country><wicri:regionArea>Muhimbili University of Health and Allied Sciences, Dar es Salaam</wicri:regionArea><wicri:noRegion>Dar es Salaam</wicri:noRegion></affiliation></author><author><name sortKey="Wahren, Britta" sort="Wahren, Britta" uniqKey="Wahren B" first="Britta" last="Wahren">Britta Wahren</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>the Swedish Institute for Infectious Disease Control, and Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Suède</country></affiliation></author><author><name sortKey="Biberfeld, Gunnel" sort="Biberfeld, Gunnel" uniqKey="Biberfeld G" first="Gunnel" last="Biberfeld">Gunnel Biberfeld</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>the Swedish Institute for Infectious Disease Control, and Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date type="published">2008</date><biblScope unit="vol">198</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1482">1482</biblScope><biblScope unit="page" to="1490">1490</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background. A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine. Methods. Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune responses were monitored with HIV-specific interferon (IFN)-γ and interleukin (IL)-2 ELISpot and lymphoproliferative assays (LPAs). Results. Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-γ responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-γ responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-γ production was detected in both the CD8+ T cell compartment (5 of 9 selected vaccinees) and the CD4+ T cell compartment (9 of 9). ELISpot results showed that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4 mg administered intramuscularly in priming for the MVA boosting vaccine. Conclusion. This HIV-DNA priming-MVA boosting approach is safe and highly immunogenic. Trials registration. International Standard Randomised Controlled Trial number: ISRCTN32604572.</div></front></TEI><affiliations><list><country><li>Suède</li><li>Tanzanie</li><li>États-Unis</li></country><region><li>Maryland</li><li>Oregon</li><li>Svealand</li></region><settlement><li>Stockholm</li></settlement></list><tree><country name="Suède"><region name="Svealand"><name sortKey="Sandstrom, Eric" sort="Sandstrom, Eric" uniqKey="Sandstrom E" first="Eric" last="Sandström">Eric Sandström</name></region><name sortKey="Biberfeld, Gunnel" sort="Biberfeld, Gunnel" uniqKey="Biberfeld G" first="Gunnel" last="Biberfeld">Gunnel Biberfeld</name><name sortKey="Birx, Deborah" sort="Birx, Deborah" uniqKey="Birx D" first="Deborah" last="Birx">Deborah Birx</name><name sortKey="Br Ve, Andreas" sort="Br Ve, Andreas" uniqKey="Br Ve A" first="Andreas" last="Br Ve">Andreas Br Ve</name><name sortKey="Bratt, Goran" sort="Bratt, Goran" uniqKey="Bratt G" first="Göran" last="Bratt">Göran Bratt</name><name sortKey="Hejdeman, Bo" sort="Hejdeman, Bo" uniqKey="Hejdeman B" first="Bo" last="Hejdeman">Bo Hejdeman</name><name sortKey="Ljungberg, Karl" sort="Ljungberg, Karl" uniqKey="Ljungberg K" first="Karl" last="Ljungberg">Karl Ljungberg</name><name sortKey="Marovich, Mary" sort="Marovich, Mary" uniqKey="Marovich M" first="Mary" last="Marovich">Mary Marovich</name><name sortKey="Nilsson, Charlotta" sort="Nilsson, Charlotta" uniqKey="Nilsson C" first="Charlotta" last="Nilsson">Charlotta Nilsson</name><name sortKey="Sandstrom, Eric" sort="Sandstrom, Eric" uniqKey="Sandstrom E" first="Eric" last="Sandström">Eric Sandström</name><name sortKey="Wahren, Britta" sort="Wahren, Britta" uniqKey="Wahren B" first="Britta" last="Wahren">Britta Wahren</name><name sortKey="Wahren, Britta" sort="Wahren, Britta" uniqKey="Wahren B" first="Britta" last="Wahren">Britta Wahren</name></country><country name="États-Unis"><region name="Maryland"><name sortKey="Robb, Merlin" sort="Robb, Merlin" uniqKey="Robb M" first="Merlin" last="Robb">Merlin Robb</name></region><name sortKey="Cox, Josephine" sort="Cox, Josephine" uniqKey="Cox J" first="Josephine" last="Cox">Josephine Cox</name><name sortKey="Earl, Patricia" sort="Earl, Patricia" uniqKey="Earl P" first="Patricia" last="Earl">Patricia Earl</name><name sortKey="Michael, Nelson" sort="Michael, Nelson" uniqKey="Michael N" first="Nelson" last="Michael">Nelson Michael</name><name sortKey="Moss, Bernard" sort="Moss, Bernard" uniqKey="Moss B" first="Bernard" last="Moss">Bernard Moss</name><name sortKey="Stout, Richard" sort="Stout, Richard" uniqKey="Stout R" first="Richard" last="Stout">Richard Stout</name><name sortKey="Vancott, Thomas" sort="Vancott, Thomas" uniqKey="Vancott T" first="Thomas" last="Vancott">Thomas Vancott</name></country><country name="Tanzanie"><noRegion><name sortKey="Aboud, Said" sort="Aboud, Said" uniqKey="Aboud S" first="Said" last="Aboud">Said Aboud</name></noRegion><name sortKey="Bakari, Muhammad" sort="Bakari, Muhammad" uniqKey="Bakari M" first="Muhammad" last="Bakari">Muhammad Bakari</name><name sortKey="Mhalu, Fred" sort="Mhalu, Fred" uniqKey="Mhalu F" first="Fred" last="Mhalu">Fred Mhalu</name><name sortKey="Pallangyo, Kisali" sort="Pallangyo, Kisali" uniqKey="Pallangyo K" first="Kisali" last="Pallangyo">Kisali Pallangyo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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