- Oral presentation
- Open Access
A first-in-man, double blind, placebo controlled study of the candidate therapeutic vaccine Opal-HIV-Gag(c) in HIV infected patients receiving HAART
© Jackson et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Good Manufacturing Practice
- Therapeutic Vaccine
- 15mer Peptide
Preclinical studies of overlapping 15mer peptides spanning SIV, SHIV or HIV pulsed autologously ex vivo have demonstrated high level, virus-specific T cells responses and viral load suppression in Macaca nemestrina. The objective of this study was to evaluate the safety and preliminary immunogenicity of Clade C consensus peptides administered ex vivo to HIV positive adults.
Synthetic 15mer peptides (n=123, Opal-HIV-Gag(c)) spanning Clade C, consensus Gag were manufactured to current good manufacturing practice and evaluated in a good laboratory practice toxicology study in Macaca mulatta. A first-in-human, single centre, placebo-controlled, double-blind, dose escalation study was conducted. Twenty three people with well controlled HIV (CD4+ > 350cells/mm3 and a HIV < 400 copies/mL), stratified by clade, were enrolled in four groups: 12mg (n=6), 24mg (n=7), 48mg (n=2) or matching placebo (n=8). Treatment was administered intravenously bedside (closed system) by enrichment of 120mL of whole blood for WBCs using a Sepax S-100 device, ex vivo mixing the peptides (or diluent alone) and incubation at 37°C for one hour prior to reinfusion. Subjects received 4 administrations at 4 weekly intervals followed by a 12 week post-treatment follow up. Immunogencity was assessed by ELIspot.
Opal-HIV-Gag(c) was generally well tolerated at doses of 12 and 24mg. There was an increased incidence of temporally associated pyrexia, chills, rigor, and transient/self-limiting lymphopenia in Opal-HIV-Gag(c) recipients compared to placebo. Only 2 subjects were recruited to the 48mg cohort. A serious adverse event of anuria, hypotension and tachycardia secondary to diarrhoea occurred following a single dose of vaccine at 48mg. No difference in ex vivo IFN-γ ELISpot response was observed at any time.
An infectious cause for the event could not be identified, leaving the possibility of immunologically-mediated reaction to the vaccine thus leading to early termination of the study.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.