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

TitlePhase I safety and immunogenicity evaluation of ADVAX, a Multigenic, DNA-based Clade C/B' HIV-1 candidate vaccine
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
P L o S One, 2010, v. 5 n. 1, article no. e8617 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/129304
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
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 FieldValueLanguage
dc.contributor.authorVasan, Sen_US
dc.contributor.authorSchlesinger, SJen_US
dc.contributor.authorHuang, Yen_US
dc.contributor.authorHurley, Aen_US
dc.contributor.authorLombardo, Aen_US
dc.contributor.authorChen, Zen_US
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.issued2010en_US
dc.identifier.citationP L o S One, 2010, v. 5 n. 1, article no. e8617en_US
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/129304-
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.languageengen_US
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 Oneen_US
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 vaccineen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1932-6203&volume=5&issue=1, article no. e8617&spage=&epage=&date=2010&atitle=Phase+I+safety+and+immunogenicity+evaluation+of+ADVAX,+a+Multigenic,+DNA-based+Clade+C/B%27+HIV-1+candidate+vaccine-
dc.identifier.emailChen, Z: zchenai@hkucc.hku.hken_US
dc.identifier.authorityChen, Z=rp00243en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0008617-
dc.identifier.pmid20111582-
dc.identifier.pmcidPMC2799527-
dc.identifier.scopuseid_2-s2.0-77952526280-
dc.identifier.hkuros176626en_US
dc.identifier.volume5en_US
dc.identifier.issue1, article no. e8617en_US
dc.identifier.isiWOS:000273896300002-

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