An HIV-1 clade A/E DNA prime, recombinant fowlpox virus boost vaccine is safe, but non-immunogenic in a randomized phase 1/11a trial in Thai volunteers at low risk of HIV infection

Background: Previously demonstrated safe and highly immunogenic in non-human primates, this study assessed DNA (pHIS-HIV-AE) prime, recombinant fowlpox (rFPV-HIV-AE) boost vaccines in humans. Results: Eight participants (6 active vaccine, 2 placebo) received all vaccinations; local and systemic reactions were mild to moderate. The percentage CD4(+) and CD8(+) T cells responding to HIV-1 Gag antigens by ICS (mean +/- SD) was 0.16 +/- 0.12 and 0.10 +/- 0.12 for active and 0.01 +/- 0.01 and 0.00 +/- 0.00 for placebo vaccine respectively. The percentage of T cells responding did not reach pre-defined thresholds to be considered positive responses. Consequently, the Data Safety Monitoring Board recommended cessation of further recruitment. Existing volunteers were followed to 52 weeks. Methods: Vectors expressing homologous HIV-1 clade A/E gag, pol, env and regulatory genes or matched placebo were administered intramuscularly at weeks 0, 4, 8 (6 mg pHIS-HIV-AE) and week 12 (3.0 x 10(8) pfu rFPV-HIV-AE) in this randomized, double-blind, placebo-controlled phase I/IIa study in healthy Thai adults at low risk of HIV infection. Immunogenicity was determined by interferon-gamma and IL-2 expression using intracellular cytokine staining assay (ICS), 13 weeks after randomization. Interim analysis was performed when eight volunteers reached 16 weeks follow-up. Conclusions: Vaccine candidates were generally well tolerated, but showed limited immunogenicity. Better vaccines and delivery systems are required.