Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption
The safety and immunogenicity of an HIV-1 nef-expressing modified vaccinia virus Ankara (MVA) was investigated in 14 HIV-1-positive patients (CD4 >400/microl) on highly active antiretroviral therapy (HAART). Patients were vaccinated at weeks 0, 4 and 16, followed by interruption of HAART at week...
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| Veröffentlicht in: | Antiviral therapy 2005-01, Vol.10 (2), p.285-300 |
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| creator | HARRER, Ellen BÄUERLE, Michael RITTMAIER, Marion EISMANN, Kathrin MÜLLER, Sandra KALDEN, Joachim R SPRIEWALD, Bernd WILLBOLD, Dieter HARRER, Thomas FERSTL, Barbara CHAPLIN, Paul PETZOLD, Barbara MATEO, Luis HANDLEY, Amanda TZATZARIS, Maria VOLLMAR, Jens BERGMANN, Silke |
| description | The safety and immunogenicity of an HIV-1 nef-expressing modified vaccinia virus Ankara (MVA) was investigated in 14 HIV-1-positive patients (CD4 >400/microl) on highly active antiretroviral therapy (HAART). Patients were vaccinated at weeks 0, 4 and 16, followed by interruption of HAART at week 18. MVA-nef was well-tolerated except for local reactions, with only mild systemic side effects reported in a few patients. Vaccination with MVA-nef was associated with recognition of new HIV-1 T-cell epitopes (cytotoxic T-lymphocyte epitopes in 9/14 patients, CD4 epitope/recombinant Nef protein in 2/14) and an increase in CD4+ and CD8+ T cells. All patients had been vaccinated against smallpox and a strong T-cell and antibody response to MVA was induced in all patients. After interruption of HAART, viral load rebounded in all patients, but after a median time of 36 (4-76) weeks in 9/14 patients, viraemia remained below the pre-HAART viral load and CD4 counts stayed above the pre-HAART levels. While six patients have remained off therapy for a median time of 64 (57-76) weeks, HAART was resumed in 8/14 patients after a median treatment interruption time of 15 (4-38) weeks. This study has demonstrated that MVA-nef is safe and immunogenic in HIV-1-infected subjects and has provided encouraging data on the potential of therapeutic vaccinations. |
| doi_str_mv | 10.1177/135965350501000212 |
| format | Article |
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Patients were vaccinated at weeks 0, 4 and 16, followed by interruption of HAART at week 18. MVA-nef was well-tolerated except for local reactions, with only mild systemic side effects reported in a few patients. Vaccination with MVA-nef was associated with recognition of new HIV-1 T-cell epitopes (cytotoxic T-lymphocyte epitopes in 9/14 patients, CD4 epitope/recombinant Nef protein in 2/14) and an increase in CD4+ and CD8+ T cells. All patients had been vaccinated against smallpox and a strong T-cell and antibody response to MVA was induced in all patients. After interruption of HAART, viral load rebounded in all patients, but after a median time of 36 (4-76) weeks in 9/14 patients, viraemia remained below the pre-HAART viral load and CD4 counts stayed above the pre-HAART levels. While six patients have remained off therapy for a median time of 64 (57-76) weeks, HAART was resumed in 8/14 patients after a median treatment interruption time of 15 (4-38) weeks. This study has demonstrated that MVA-nef is safe and immunogenic in HIV-1-infected subjects and has provided encouraging data on the potential of therapeutic vaccinations.</description><identifier>ISSN: 1359-6535</identifier><identifier>EISSN: 2040-2058</identifier><identifier>DOI: 10.1177/135965350501000212</identifier><identifier>PMID: 15865223</identifier><language>eng</language><publisher>London: International Medical Press</publisher><subject>Adult ; AIDS Vaccines - administration & dosage ; AIDS Vaccines - therapeutic use ; Amino Acid Sequence ; Anti-Retroviral Agents - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antibodies, Viral - blood ; Antibody Specificity ; Antiretroviral Therapy, Highly Active ; Antiviral agents ; Biological and medical sciences ; CD4 Antigens - immunology ; Drug Administration Schedule ; Epitopes - immunology ; Gene Products, nef - genetics ; Genetic Vectors ; HIV Seropositivity - drug therapy ; HIV Seropositivity - immunology ; HIV Seropositivity - therapy ; HIV Seropositivity - virology ; HIV-1 - genetics ; HIV-1 - isolation & purification ; Humans ; Immunotherapy ; Lymphocyte Count ; Medical sciences ; Middle Aged ; Molecular Sequence Data ; nef Gene Products, Human Immunodeficiency Virus ; Pharmacology. Drug treatments ; Sequence Alignment ; T-Lymphocytes, Cytotoxic - immunology ; Vaccines, Synthetic - administration & dosage ; Vaccines, Synthetic - immunology ; Vaccines, Synthetic - therapeutic use ; Vaccinia virus - genetics ; Vaccinia virus - immunology ; Viral Load ; Withholding Treatment</subject><ispartof>Antiviral therapy, 2005-01, Vol.10 (2), p.285-300</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-4351e741968cafb9a74720d4e4c082b037b2094c06bdfcfb4c5ced52940b0b733</citedby><cites>FETCH-LOGICAL-c375t-4351e741968cafb9a74720d4e4c082b037b2094c06bdfcfb4c5ced52940b0b733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16715819$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15865223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HARRER, Ellen</creatorcontrib><creatorcontrib>BÄUERLE, Michael</creatorcontrib><creatorcontrib>RITTMAIER, Marion</creatorcontrib><creatorcontrib>EISMANN, Kathrin</creatorcontrib><creatorcontrib>MÜLLER, Sandra</creatorcontrib><creatorcontrib>KALDEN, Joachim R</creatorcontrib><creatorcontrib>SPRIEWALD, Bernd</creatorcontrib><creatorcontrib>WILLBOLD, Dieter</creatorcontrib><creatorcontrib>HARRER, Thomas</creatorcontrib><creatorcontrib>FERSTL, Barbara</creatorcontrib><creatorcontrib>CHAPLIN, Paul</creatorcontrib><creatorcontrib>PETZOLD, Barbara</creatorcontrib><creatorcontrib>MATEO, Luis</creatorcontrib><creatorcontrib>HANDLEY, Amanda</creatorcontrib><creatorcontrib>TZATZARIS, Maria</creatorcontrib><creatorcontrib>VOLLMAR, Jens</creatorcontrib><creatorcontrib>BERGMANN, Silke</creatorcontrib><title>Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption</title><title>Antiviral therapy</title><addtitle>Antivir Ther</addtitle><description>The safety and immunogenicity of an HIV-1 nef-expressing modified vaccinia virus Ankara (MVA) was investigated in 14 HIV-1-positive patients (CD4 >400/microl) on highly active antiretroviral therapy (HAART). Patients were vaccinated at weeks 0, 4 and 16, followed by interruption of HAART at week 18. MVA-nef was well-tolerated except for local reactions, with only mild systemic side effects reported in a few patients. Vaccination with MVA-nef was associated with recognition of new HIV-1 T-cell epitopes (cytotoxic T-lymphocyte epitopes in 9/14 patients, CD4 epitope/recombinant Nef protein in 2/14) and an increase in CD4+ and CD8+ T cells. All patients had been vaccinated against smallpox and a strong T-cell and antibody response to MVA was induced in all patients. After interruption of HAART, viral load rebounded in all patients, but after a median time of 36 (4-76) weeks in 9/14 patients, viraemia remained below the pre-HAART viral load and CD4 counts stayed above the pre-HAART levels. While six patients have remained off therapy for a median time of 64 (57-76) weeks, HAART was resumed in 8/14 patients after a median treatment interruption time of 15 (4-38) weeks. This study has demonstrated that MVA-nef is safe and immunogenic in HIV-1-infected subjects and has provided encouraging data on the potential of therapeutic vaccinations.</description><subject>Adult</subject><subject>AIDS Vaccines - administration & dosage</subject><subject>AIDS Vaccines - therapeutic use</subject><subject>Amino Acid Sequence</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antibodies, Viral - blood</subject><subject>Antibody Specificity</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>CD4 Antigens - immunology</subject><subject>Drug Administration Schedule</subject><subject>Epitopes - immunology</subject><subject>Gene Products, nef - genetics</subject><subject>Genetic Vectors</subject><subject>HIV Seropositivity - drug therapy</subject><subject>HIV Seropositivity - immunology</subject><subject>HIV Seropositivity - therapy</subject><subject>HIV Seropositivity - virology</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - isolation & purification</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Lymphocyte Count</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>nef Gene Products, Human Immunodeficiency Virus</subject><subject>Pharmacology. Drug treatments</subject><subject>Sequence Alignment</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Vaccines, Synthetic - administration & dosage</subject><subject>Vaccines, Synthetic - immunology</subject><subject>Vaccines, Synthetic - therapeutic use</subject><subject>Vaccinia virus - genetics</subject><subject>Vaccinia virus - immunology</subject><subject>Viral Load</subject><subject>Withholding Treatment</subject><issn>1359-6535</issn><issn>2040-2058</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkc1u1DAURi0EokPhBVggb-iKgH_jhN2ogk6lIiQ0dBvZznVrlDjBdgrzaLxdHc1IXbCyrHvOd6_0IfSWko-UKvWJctnWkksiCSWEMMqeoQ0jglSMyOY52qxAtRJn6FVKvwrStIS8RGdUNrVkjG_Qv_09RD3Dkr3FD9paH3T2U8CTw7vr24pWPjiwGXo8lwGEnHCZ7rbbH3v8x-d7rHEEO42miCEfHRzAVfB3jpCSD3f42-32M07aQT58wH4clzDdQfDW5wPWocdlxbBAsLBGP_ioBzxMusf9Elc9R9B5LKsLmCHGZV4vfI1eOD0keHN6z9HPr1_2l7vq5vvV9eX2prJcyVwJLikoQdu6sdqZViuhGOkFCEsaZghXhpG2fGrTO-uMsNJCL1kriCFGcX6OLo65c5x-L5ByN_pkYRh0gGlJXa2UaoRcQXYEbZxSiuC6OfpRx0NHSbcW1v1fWJHendIXM0L_pJwaKsD7E6CT1YOLOlifnrhaFZS2_BElO5_k</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>HARRER, Ellen</creator><creator>BÄUERLE, Michael</creator><creator>RITTMAIER, Marion</creator><creator>EISMANN, Kathrin</creator><creator>MÜLLER, Sandra</creator><creator>KALDEN, Joachim R</creator><creator>SPRIEWALD, Bernd</creator><creator>WILLBOLD, Dieter</creator><creator>HARRER, Thomas</creator><creator>FERSTL, Barbara</creator><creator>CHAPLIN, Paul</creator><creator>PETZOLD, Barbara</creator><creator>MATEO, Luis</creator><creator>HANDLEY, Amanda</creator><creator>TZATZARIS, Maria</creator><creator>VOLLMAR, Jens</creator><creator>BERGMANN, Silke</creator><general>International Medical Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20050101</creationdate><title>Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption</title><author>HARRER, Ellen ; BÄUERLE, Michael ; RITTMAIER, Marion ; EISMANN, Kathrin ; MÜLLER, Sandra ; KALDEN, Joachim R ; SPRIEWALD, Bernd ; WILLBOLD, Dieter ; HARRER, Thomas ; FERSTL, Barbara ; CHAPLIN, Paul ; PETZOLD, Barbara ; MATEO, Luis ; HANDLEY, Amanda ; TZATZARIS, Maria ; VOLLMAR, Jens ; BERGMANN, Silke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-4351e741968cafb9a74720d4e4c082b037b2094c06bdfcfb4c5ced52940b0b733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>AIDS Vaccines - administration & dosage</topic><topic>AIDS Vaccines - therapeutic use</topic><topic>Amino Acid Sequence</topic><topic>Anti-Retroviral Agents - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antibodies, Viral - blood</topic><topic>Antibody Specificity</topic><topic>Antiretroviral Therapy, Highly Active</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>CD4 Antigens - immunology</topic><topic>Drug Administration Schedule</topic><topic>Epitopes - immunology</topic><topic>Gene Products, nef - genetics</topic><topic>Genetic Vectors</topic><topic>HIV Seropositivity - drug therapy</topic><topic>HIV Seropositivity - immunology</topic><topic>HIV Seropositivity - therapy</topic><topic>HIV Seropositivity - virology</topic><topic>HIV-1 - genetics</topic><topic>HIV-1 - isolation & purification</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Lymphocyte Count</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>nef Gene Products, Human Immunodeficiency Virus</topic><topic>Pharmacology. 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Patients were vaccinated at weeks 0, 4 and 16, followed by interruption of HAART at week 18. MVA-nef was well-tolerated except for local reactions, with only mild systemic side effects reported in a few patients. Vaccination with MVA-nef was associated with recognition of new HIV-1 T-cell epitopes (cytotoxic T-lymphocyte epitopes in 9/14 patients, CD4 epitope/recombinant Nef protein in 2/14) and an increase in CD4+ and CD8+ T cells. All patients had been vaccinated against smallpox and a strong T-cell and antibody response to MVA was induced in all patients. After interruption of HAART, viral load rebounded in all patients, but after a median time of 36 (4-76) weeks in 9/14 patients, viraemia remained below the pre-HAART viral load and CD4 counts stayed above the pre-HAART levels. While six patients have remained off therapy for a median time of 64 (57-76) weeks, HAART was resumed in 8/14 patients after a median treatment interruption time of 15 (4-38) weeks. This study has demonstrated that MVA-nef is safe and immunogenic in HIV-1-infected subjects and has provided encouraging data on the potential of therapeutic vaccinations.</abstract><cop>London</cop><pub>International Medical Press</pub><pmid>15865223</pmid><doi>10.1177/135965350501000212</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Antiviral therapy, 2005-01, Vol.10 (2), p.285-300 |
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| subjects | Adult AIDS Vaccines - administration & dosage AIDS Vaccines - therapeutic use Amino Acid Sequence Anti-Retroviral Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antibodies, Viral - blood Antibody Specificity Antiretroviral Therapy, Highly Active Antiviral agents Biological and medical sciences CD4 Antigens - immunology Drug Administration Schedule Epitopes - immunology Gene Products, nef - genetics Genetic Vectors HIV Seropositivity - drug therapy HIV Seropositivity - immunology HIV Seropositivity - therapy HIV Seropositivity - virology HIV-1 - genetics HIV-1 - isolation & purification Humans Immunotherapy Lymphocyte Count Medical sciences Middle Aged Molecular Sequence Data nef Gene Products, Human Immunodeficiency Virus Pharmacology. Drug treatments Sequence Alignment T-Lymphocytes, Cytotoxic - immunology Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - immunology Vaccines, Synthetic - therapeutic use Vaccinia virus - genetics Vaccinia virus - immunology Viral Load Withholding Treatment |
| title | Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption |
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