Article: Phase I safety and immunogenicity evaluation of ADVAX, a Multigenic, DNA-based Clade C/B' HIV-1 candidate vaccine

File Download Links for fulltext
(May Require Subscription)
Supplementary
  • Basic View
  • Metadata View
  • XML View
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
2011 Impact Factor: 4.092
2011 SCImago Journal Rankings: 0.519
DOIhttp://dx.doi.org/10.1371/journal.pone.0008617
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.

PubMed Central IDPMC2799527
DC Field
Value
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
2011 Impact Factor: 4.092
2011 SCImago Journal Rankings: 0.519
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
Author Affiliations
  1. Aaron Diamond AIDS Research Center