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Article: Phase I safety and immunogenicity evaluation of ADVAX, a Multigenic, DNA-based Clade C/B' HIV-1 candidate vaccine
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TitlePhase I safety and immunogenicity evaluation of ADVAX, a Multigenic, DNA-based Clade C/B' HIV-1 candidate vaccine
 
AuthorsVasan, S1
Schlesinger, SJ1
Huang, Y1
Hurley, A1
Lombardo, A1
Chen, Z1
Than, S1
Adesanya, P1
Bunce, C1
Boaz, M1
Boyle, R1
Sayeed, E1
Clark, L1
Dugin, D1
Schmidt, C1
Song, Y1
Seamons, L1
Dally, L1
Ho, M1
Smith, C1
Markowitz, M1
Cox, J1
Gill, DK1
Gilmour, J1
Keefer, MC1
Fast, P1
Ho, DD1
 
Issue Date2010
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationP L o S One, 2010, v. 5 n. 1, article no. e8617 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0008617
 
AbstractBACKGROUND: We conducted a Phase I dose escalation trial of ADVAX, a DNA-based candidate HIV-1 vaccine expressing Clade C/B' env, gag, pol, nef, and tat genes. Sequences were derived from a prevalent circulating recombinant form in Yunnan, China, an area of high HIV-1 incidence. The objective was to evaluate the safety and immunogenicity of ADVAX in human volunteers. METHODOLOGY/PRINCIPAL FINDINGS: ADVAX or placebo was administered intramuscularly at months 0, 1 and 3 to 45 healthy volunteers not at high risk for HIV-1. Three dosage levels [0.2 mg (low), 1.0 mg (mid), and 4.0 mg (high)] were tested. Twelve volunteers in each dosage group were assigned to receive ADVAX and three to receive placebo in a double-blind design. Subjects were followed for local and systemic reactogenicity, adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. ADVAX was safe and well-tolerated, with no vaccine-related serious adverse events. Local and systemic reactogenicity events were reported by 64% and 42% of vaccine recipients, respectively. The majority of events were mild. The IFNgamma ELISpot response rates to any HIV antigen were 0/9 (0%) in the placebo group, 3/12 (25%) in the low-dosage group, 4/12 (33%) in the mid-dosage group, and 2/12 (17%) in the high-dosage group. Overall, responses were generally transient and occurred to each gene product, although volunteers responded to single antigens only. Binding antibodies to gp120 were not detected in any volunteers, and HIV seroconversion did not occur. CONCLUSIONS/SIGNIFICANCE: ADVAX delivered intramuscularly is safe, well-tolerated, and elicits modest but transient cellular immune responses. TRIAL REGISTRATION: Clinicaltrials.gov NCT00249106.
 
ISSN1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0008617
 
PubMed Central IDPMC2799527
 
ISI Accession Number IDWOS:000273896300002
Funding AgencyGrant Number
International AIDS Vaccine Initiative (IAVI)
United States for International Development (USAID)
Rockefeller University
University of Rochester Clinical and Translational Science
Funding Information:

Funding for this study was provided by the International AIDS Vaccine Initiative (IAVI) and its donors, including the generous support of the American people through the United States for International Development (USAID). IAVI played a direct role in study design, data collection and analysis, decision to publish, and preparation of this manuscript. Support was also provided by the Rockefeller University and University of Rochester Clinical and Translational Science Awards.

 
DC FieldValue
dc.contributor.authorVasan, S
 
dc.contributor.authorSchlesinger, SJ
 
dc.contributor.authorHuang, Y
 
dc.contributor.authorHurley, A
 
dc.contributor.authorLombardo, A
 
dc.contributor.authorChen, Z
 
dc.contributor.authorThan, S
 
dc.contributor.authorAdesanya, P
 
dc.contributor.authorBunce, C
 
dc.contributor.authorBoaz, M
 
dc.contributor.authorBoyle, R
 
dc.contributor.authorSayeed, E
 
dc.contributor.authorClark, L
 
dc.contributor.authorDugin, D
 
dc.contributor.authorSchmidt, C
 
dc.contributor.authorSong, Y
 
dc.contributor.authorSeamons, L
 
dc.contributor.authorDally, L
 
dc.contributor.authorHo, M
 
dc.contributor.authorSmith, C
 
dc.contributor.authorMarkowitz, M
 
dc.contributor.authorCox, J
 
dc.contributor.authorGill, DK
 
dc.contributor.authorGilmour, J
 
dc.contributor.authorKeefer, MC
 
dc.contributor.authorFast, P
 
dc.contributor.authorHo, DD
 
dc.date.accessioned2010-12-23T08:34:57Z
 
dc.date.available2010-12-23T08:34:57Z
 
dc.date.issued2010
 
dc.description.abstractBACKGROUND: We conducted a Phase I dose escalation trial of ADVAX, a DNA-based candidate HIV-1 vaccine expressing Clade C/B' env, gag, pol, nef, and tat genes. Sequences were derived from a prevalent circulating recombinant form in Yunnan, China, an area of high HIV-1 incidence. The objective was to evaluate the safety and immunogenicity of ADVAX in human volunteers. METHODOLOGY/PRINCIPAL FINDINGS: ADVAX or placebo was administered intramuscularly at months 0, 1 and 3 to 45 healthy volunteers not at high risk for HIV-1. Three dosage levels [0.2 mg (low), 1.0 mg (mid), and 4.0 mg (high)] were tested. Twelve volunteers in each dosage group were assigned to receive ADVAX and three to receive placebo in a double-blind design. Subjects were followed for local and systemic reactogenicity, adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. ADVAX was safe and well-tolerated, with no vaccine-related serious adverse events. Local and systemic reactogenicity events were reported by 64% and 42% of vaccine recipients, respectively. The majority of events were mild. The IFNgamma ELISpot response rates to any HIV antigen were 0/9 (0%) in the placebo group, 3/12 (25%) in the low-dosage group, 4/12 (33%) in the mid-dosage group, and 2/12 (17%) in the high-dosage group. Overall, responses were generally transient and occurred to each gene product, although volunteers responded to single antigens only. Binding antibodies to gp120 were not detected in any volunteers, and HIV seroconversion did not occur. CONCLUSIONS/SIGNIFICANCE: ADVAX delivered intramuscularly is safe, well-tolerated, and elicits modest but transient cellular immune responses. TRIAL REGISTRATION: Clinicaltrials.gov NCT00249106.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationP L o S One, 2010, v. 5 n. 1, article no. e8617 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0008617
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0008617
 
dc.identifier.hkuros176626
 
dc.identifier.isiWOS:000273896300002
Funding AgencyGrant Number
International AIDS Vaccine Initiative (IAVI)
United States for International Development (USAID)
Rockefeller University
University of Rochester Clinical and Translational Science
Funding Information:

Funding for this study was provided by the International AIDS Vaccine Initiative (IAVI) and its donors, including the generous support of the American people through the United States for International Development (USAID). IAVI played a direct role in study design, data collection and analysis, decision to publish, and preparation of this manuscript. Support was also provided by the Rockefeller University and University of Rochester Clinical and Translational Science Awards.

 
dc.identifier.issn1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
dc.identifier.issue1, article no. e8617
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC2799527
 
dc.identifier.pmid20111582
 
dc.identifier.scopuseid_2-s2.0-77952526280
 
dc.identifier.urihttp://hdl.handle.net/10722/129304
 
dc.identifier.volume5
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.relation.ispartofP L o S One
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshAIDS Vaccines - administration and dosage - adverse effects - immunology
 
dc.subject.meshDose-Response Relationship, Immunologic
 
dc.subject.meshEnzyme-Linked Immunosorbent Assay
 
dc.subject.meshHIV Antibodies - biosynthesis
 
dc.subject.meshHIV-1 - genetics - immunology
 
dc.titlePhase I safety and immunogenicity evaluation of ADVAX, a Multigenic, DNA-based Clade C/B' HIV-1 candidate vaccine
 
dc.typeArticle
 
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<contributor.author>Hurley, A</contributor.author>
<contributor.author>Lombardo, A</contributor.author>
<contributor.author>Chen, Z</contributor.author>
<contributor.author>Than, S</contributor.author>
<contributor.author>Adesanya, P</contributor.author>
<contributor.author>Bunce, C</contributor.author>
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<contributor.author>Sayeed, E</contributor.author>
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<contributor.author>Keefer, MC</contributor.author>
<contributor.author>Fast, P</contributor.author>
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<date.accessioned>2010-12-23T08:34:57Z</date.accessioned>
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<description.abstract>BACKGROUND: We conducted a Phase I dose escalation trial of ADVAX, a DNA-based candidate HIV-1 vaccine expressing Clade C/B&apos; env, gag, pol, nef, and tat genes. Sequences were derived from a prevalent circulating recombinant form in Yunnan, China, an area of high HIV-1 incidence. The objective was to evaluate the safety and immunogenicity of ADVAX in human volunteers. METHODOLOGY/PRINCIPAL FINDINGS: ADVAX or placebo was administered intramuscularly at months 0, 1 and 3 to 45 healthy volunteers not at high risk for HIV-1. Three dosage levels [0.2 mg (low), 1.0 mg (mid), and 4.0 mg (high)] were tested. Twelve volunteers in each dosage group were assigned to receive ADVAX and three to receive placebo in a double-blind design. Subjects were followed for local and systemic reactogenicity, adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. ADVAX was safe and well-tolerated, with no vaccine-related serious adverse events. Local and systemic reactogenicity events were reported by 64% and 42% of vaccine recipients, respectively. The majority of events were mild. The IFNgamma ELISpot response rates to any HIV antigen were 0/9 (0%) in the placebo group, 3/12 (25%) in the low-dosage group, 4/12 (33%) in the mid-dosage group, and 2/12 (17%) in the high-dosage group. Overall, responses were generally transient and occurred to each gene product, although volunteers responded to single antigens only. Binding antibodies to gp120 were not detected in any volunteers, and HIV seroconversion did not occur. CONCLUSIONS/SIGNIFICANCE: ADVAX delivered intramuscularly is safe, well-tolerated, and elicits modest but transient cellular immune responses. TRIAL REGISTRATION: Clinicaltrials.gov NCT00249106.</description.abstract>
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Author Affiliations
  1. Aaron Diamond AIDS Research Center