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Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers
Abstract An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of human immunodeficiency virus type-1 (HIV-1)-specific...
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| Published in: | Vaccine 2008-07, Vol.26 (31), p.3947-3957 |
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| cites | cdi_FETCH-LOGICAL-c4630-6d7893471bb0674e545a377dd9b89cc261b0d81d068500dd6982d7d1f9923d093 |
| container_end_page | 3957 |
| container_issue | 31 |
| container_start_page | 3947 |
| container_title | Vaccine |
| container_volume | 26 |
| creator | Wang, Shixia Kennedy, Jeffrey S West, Kim Montefiori, David C Coley, Scott Lawrence, John Shen, Siyuan Green, Sharone Rothman, Alan L Ennis, Francis A Arthos, James Pal, Ranajit Markham, Phillip Lu, Shan |
| description | Abstract An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of human immunodeficiency virus type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime–protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial. Robust cross-subtype HIV-1-specific T cell responses were detected in IFN-γ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime–protein boost approach is an effective immunization method to elicit both humoral and cell-mediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds. |
| doi_str_mv | 10.1016/j.vaccine.2007.12.060 |
| format | article |
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Here we report on the induction of human immunodeficiency virus type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime–protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial. Robust cross-subtype HIV-1-specific T cell responses were detected in IFN-γ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime–protein boost approach is an effective immunization method to elicit both humoral and cell-mediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2007.12.060</identifier><identifier>PMID: 18724414</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Acquired immune deficiency syndrome ; Adolescent ; Adult ; AIDS ; AIDS Vaccines - immunology ; Allergy and Immunology ; Antigens ; Clinical trials ; Cross Reactions ; Deoxyribonucleic acid ; DNA ; DNA vaccine ; Female ; HIV ; HIV Antibodies - blood ; HIV-1 ; HIV-1 - immunology ; Human Experimentation ; Human immunodeficiency virus ; Humans ; Immunization ; Immunization, Secondary ; Interferon-gamma - metabolism ; Male ; Middle Aged ; Neutralization Tests ; Phase I clinical trial ; Plasmids ; Prime–boost ; Proteins ; Recombinant protein vaccine ; Studies ; T-Lymphocytes - immunology ; Vaccines ; Vaccines, DNA - immunology ; Vaccines, Subunit - immunology</subject><ispartof>Vaccine, 2008-07, Vol.26 (31), p.3947-3957</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><rights>Copyright Elsevier Limited Jul 23, 2008</rights><rights>2008 Elsevier Ltd. All rights reserved. 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4630-6d7893471bb0674e545a377dd9b89cc261b0d81d068500dd6982d7d1f9923d093</citedby><cites>FETCH-LOGICAL-c4630-6d7893471bb0674e545a377dd9b89cc261b0d81d068500dd6982d7d1f9923d093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18724414$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Shixia</creatorcontrib><creatorcontrib>Kennedy, Jeffrey S</creatorcontrib><creatorcontrib>West, Kim</creatorcontrib><creatorcontrib>Montefiori, David C</creatorcontrib><creatorcontrib>Coley, Scott</creatorcontrib><creatorcontrib>Lawrence, John</creatorcontrib><creatorcontrib>Shen, Siyuan</creatorcontrib><creatorcontrib>Green, Sharone</creatorcontrib><creatorcontrib>Rothman, Alan L</creatorcontrib><creatorcontrib>Ennis, Francis A</creatorcontrib><creatorcontrib>Arthos, James</creatorcontrib><creatorcontrib>Pal, Ranajit</creatorcontrib><creatorcontrib>Markham, Phillip</creatorcontrib><creatorcontrib>Lu, Shan</creatorcontrib><title>Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of human immunodeficiency virus type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime–protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial. Robust cross-subtype HIV-1-specific T cell responses were detected in IFN-γ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime–protein boost approach is an effective immunization method to elicit both humoral and cell-mediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adolescent</subject><subject>Adult</subject><subject>AIDS</subject><subject>AIDS Vaccines - immunology</subject><subject>Allergy and Immunology</subject><subject>Antigens</subject><subject>Clinical trials</subject><subject>Cross Reactions</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA vaccine</subject><subject>Female</subject><subject>HIV</subject><subject>HIV Antibodies - blood</subject><subject>HIV-1</subject><subject>HIV-1 - immunology</subject><subject>Human Experimentation</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunization, Secondary</subject><subject>Interferon-gamma - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neutralization Tests</subject><subject>Phase I clinical trial</subject><subject>Plasmids</subject><subject>Prime–boost</subject><subject>Proteins</subject><subject>Recombinant protein vaccine</subject><subject>Studies</subject><subject>T-Lymphocytes - immunology</subject><subject>Vaccines</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccines, Subunit - immunology</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqFks1u1DAUhSMEosPAI4AsIbHLcJ04TrIpqoafVqpgwY_YWY59h_GQ2KmdjJRdH6ESb8iT4DAjCt2wsiV_5_rce26SPKWwokD5y91qL5UyFlcZQLmi2Qo43EsWtCrzNCtodT9ZQMZZyih8PUkehbADgCKn9cPkJEIZY5Qtkpu1dyGkYWyGqUci7WAap6d40URh246t9MR03WiReAy9swEDMVaPCjVpIkh610572aIdyOv3Z6T3psOf1z967wY0ljTOhYGcX3xJKTlajnqyRdkO24lsx05asnftaAdEHx4nDzayDfjkeC6Tz2_ffFqfp5cf3l2szy5TxXgOKddlVeespE0DvGRYsELmZal13VS1UhmnDeiKauBVAaA1r6tMl5pu6jrLNdT5Mjk91O3HpkOton0vWzG7l34SThrx74s1W_HN7UVeshzikJfJi2MB765GDIPoTJhHJi26MQheMw6snsHnd8CdG72NzQlaFFXFyvw3VRwoNQficfPHCgUxJy524jg-MScuaCZi4lH37O8-blXHiCPw6gBgnObeoBdBGbQxPuNRDUI7898vTu9UUK2xRsn2O04YbrsRIQrEx3nt5q2DCoCVGc9_AQfy15Q</recordid><startdate>20080723</startdate><enddate>20080723</enddate><creator>Wang, Shixia</creator><creator>Kennedy, Jeffrey S</creator><creator>West, Kim</creator><creator>Montefiori, David C</creator><creator>Coley, Scott</creator><creator>Lawrence, John</creator><creator>Shen, Siyuan</creator><creator>Green, Sharone</creator><creator>Rothman, Alan L</creator><creator>Ennis, Francis A</creator><creator>Arthos, James</creator><creator>Pal, Ranajit</creator><creator>Markham, Phillip</creator><creator>Lu, Shan</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080723</creationdate><title>Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers</title><author>Wang, Shixia ; Kennedy, Jeffrey S ; West, Kim ; Montefiori, David C ; Coley, Scott ; Lawrence, John ; Shen, Siyuan ; Green, Sharone ; Rothman, Alan L ; Ennis, Francis A ; Arthos, James ; Pal, Ranajit ; Markham, Phillip ; Lu, Shan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4630-6d7893471bb0674e545a377dd9b89cc261b0d81d068500dd6982d7d1f9923d093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adolescent</topic><topic>Adult</topic><topic>AIDS</topic><topic>AIDS Vaccines - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Shixia</au><au>Kennedy, Jeffrey S</au><au>West, Kim</au><au>Montefiori, David C</au><au>Coley, Scott</au><au>Lawrence, John</au><au>Shen, Siyuan</au><au>Green, Sharone</au><au>Rothman, Alan L</au><au>Ennis, Francis A</au><au>Arthos, James</au><au>Pal, Ranajit</au><au>Markham, Phillip</au><au>Lu, Shan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2008-07-23</date><risdate>2008</risdate><volume>26</volume><issue>31</issue><spage>3947</spage><epage>3957</epage><pages>3947-3957</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>Abstract An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of human immunodeficiency virus type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime–protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial. Robust cross-subtype HIV-1-specific T cell responses were detected in IFN-γ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime–protein boost approach is an effective immunization method to elicit both humoral and cell-mediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>18724414</pmid><doi>10.1016/j.vaccine.2007.12.060</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Vaccine, 2008-07, Vol.26 (31), p.3947-3957 |
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| subjects | Acquired immune deficiency syndrome Adolescent Adult AIDS AIDS Vaccines - immunology Allergy and Immunology Antigens Clinical trials Cross Reactions Deoxyribonucleic acid DNA DNA vaccine Female HIV HIV Antibodies - blood HIV-1 HIV-1 - immunology Human Experimentation Human immunodeficiency virus Humans Immunization Immunization, Secondary Interferon-gamma - metabolism Male Middle Aged Neutralization Tests Phase I clinical trial Plasmids Prime–boost Proteins Recombinant protein vaccine Studies T-Lymphocytes - immunology Vaccines Vaccines, DNA - immunology Vaccines, Subunit - immunology |
| title | Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers |
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