A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204)

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dc.contributor.authorChurchyard, Gavin Jen_ZA
dc.contributor.authorMorgan, Ceciliaen_ZA
dc.contributor.authorAdams, Elizabethen_ZA
dc.contributor.authorHural, Johnen_ZA
dc.contributor.authorGraham, Barney Sen_ZA
dc.contributor.authorMoodie, Zoeen_ZA
dc.contributor.authorGrove, Dougen_ZA
dc.contributor.authorGray, Glendaen_ZA
dc.contributor.authorBekker, Linda-Gailen_ZA
dc.contributor.authorMcElrath, M Julianaen_ZA
dc.date.accessioned2015-11-23T12:25:43Z
dc.date.available2015-11-23T12:25:43Z
dc.date.issued2011en_ZA
dc.description.abstractBACKGROUND: The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean. METHODS: 480 participants were evenly randomized to receive either: DNA (4 mg IM by Biojector) at 0, 1 and 2 months, followed by rAd5 (10 10 PU IM by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost. RESULTS: The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients. CONCLUSION: The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies. Trial Registration: ClinicalTrials.gov NCT00125970en_ZA
dc.identifier.apacitationChurchyard, G. J., Morgan, C., Adams, E., Hural, J., Graham, B. S., Moodie, Z., ... McElrath, M. J. (2011). A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204). <i>PLoS One</i>, http://hdl.handle.net/11427/15280en_ZA
dc.identifier.chicagocitationChurchyard, Gavin J, Cecilia Morgan, Elizabeth Adams, John Hural, Barney S Graham, Zoe Moodie, Doug Grove, Glenda Gray, Linda-Gail Bekker, and M Juliana McElrath "A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204)." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/15280en_ZA
dc.identifier.citationChurchyard, G. J., Morgan, C., Adams, E., Hural, J., Graham, B. S., Moodie, Z., ... & Keefer, M. C. (2011). A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204). PloS one, 6(8), e21225. doi:10.1371/journal.pone.0021225en_ZA
dc.identifier.ris TY - Journal Article AU - Churchyard, Gavin J AU - Morgan, Cecilia AU - Adams, Elizabeth AU - Hural, John AU - Graham, Barney S AU - Moodie, Zoe AU - Grove, Doug AU - Gray, Glenda AU - Bekker, Linda-Gail AU - McElrath, M Juliana AB - BACKGROUND: The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean. METHODS: 480 participants were evenly randomized to receive either: DNA (4 mg IM by Biojector) at 0, 1 and 2 months, followed by rAd5 (10 10 PU IM by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost. RESULTS: The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients. CONCLUSION: The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies. Trial Registration: ClinicalTrials.gov NCT00125970 DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0021225 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204) TI - A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204) UR - http://hdl.handle.net/11427/15280 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15280
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0021225
dc.identifier.vancouvercitationChurchyard GJ, Morgan C, Adams E, Hural J, Graham BS, Moodie Z, et al. A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204). PLoS One. 2011; http://hdl.handle.net/11427/15280.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDesmond Tutu HIV Centreen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2011 Churchyard et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherVaccinesen_ZA
dc.subject.otherCytotoxic T cellsen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherAntibodiesen_ZA
dc.subject.otherAntibody responseen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherHIV-1en_ZA
dc.titleA phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204)en_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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