Author
Listed:
- Akil Jackson
- Henrik N Kløverpris
- Marta Boffito
- Amanda Handley
- Mark Atkins
- Peter Hayes
- Jill Gilmour
- Lynn Riddel
- Fabian Chen
- Melanie Bailey-Tippets
- Bruce Walker
- Jim Ackland
- Mark Sullivan
- Philip Goulder
Abstract
Background: Preclinical studies of overlapping 15mer peptides, spanning SIV, SHIV or HIV, pulsed on autologous PBMC ex vivo have demonstrated high level, virus-specific T cell responses and viral suppression in non-human primates (NHP). Opal-HIV-Gag(c) consists of 120 synthetic 15mer peptides spanning Clade C, consensus Gag, manufactured to current good manufacturing practice; having been evaluated in a good laboratory practice toxicology study in Macaca mulatta. We evaluated the safety and preliminary immunogenicity of such peptides administered intravenously after short-duration ex vivo incubation, to HIV-positive adults on suppressive antiretroviral therapy. Methods and Findings: A first-in-human, placebo-controlled, double-blind, dose escalation study was conducted. Twenty-three patients with virus suppressed by antiretroviral therapy were enrolled in four groups 12 mg (n = 6), 24 mg (n = 6), 48 mg (n = 2) or matching placebo (n = 8). Treatment was administered intravenously after bedside enrichment of 120 mL whole blood for white cells using a closed system (Sepax S-100 device), with ex vivo peptide admixture (or diluent alone) and 37°C incubation for one hour prior to reinfusion. Patients received 4 administrations at monthly intervals followed by a 12-week observation post-treatment. Opal-HIV-Gag(c) was reasonably tolerated at doses of 12 and 24 mg. There was an increased incidence of temporally associated pyrexia, chills, and transient/self-limiting lymphopenia in Opal-HIV-Gag(c) recipients compared to placebo. The study was terminated early, after two patients were recruited to the 48 mg cohort; a serious adverse event of hypotension, tachycardia secondary to diarrhoea occurred following a single product administration. An infectious cause for the event could not be identified, leaving the possibility of immunologically mediated product reaction. Conclusions: A serious, potentially life-threatening event of hypotension led to early, precautionary termination of the study. In the absence of a clearly defined mechanism or ability to predict such occurrence, further development of Opal-HIV-Gag(c) will not be undertaken in the current form. Registration: ClinicalTrials.gov NCT01123915; EudraCT: 2008-005142-23
Suggested Citation
Akil Jackson & Henrik N Kløverpris & Marta Boffito & Amanda Handley & Mark Atkins & Peter Hayes & Jill Gilmour & Lynn Riddel & Fabian Chen & Melanie Bailey-Tippets & Bruce Walker & Jim Ackland & Mark , 2013.
"A Randomised, Placebo-Controlled, First-In-Human Study of a Novel Clade C Therapeutic Peptide Vaccine Administered Ex Vivo to Autologous White Blood Cells in HIV Infected Individuals,"
PLOS ONE, Public Library of Science, vol. 8(9), pages 1-5, September.
Handle:
RePEc:plo:pone00:0073765
DOI: 10.1371/journal.pone.0073765
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