Abstract: | BackgroundDNA-based vaccines have been safe but weakly immunogenic in humans to
date.Methods and FindingsWe sought to determine the safety, tolerability, and immunogenicity of ADVAX,
a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by
in vivo electroporation (EP) in a Phase-1,
double-blind, randomized placebo-controlled trial in healthy volunteers.
Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo
via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8.
A third vaccination was administered to eleven volunteers at week 36. EP was
safe, well-tolerated and considered acceptable for a prophylactic vaccine.
EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated
immunity by up to 70-fold over IM injection, as measured by gamma interferon
ELISpot. The number of antigens to which the response was detected improved
with EP and increasing dosage. Intracellular cytokine staining analysis of
ELISpot responders revealed both CD4+ and CD8+ T cell responses,
with co-secretion of multiple cytokines.ConclusionsThis is the first demonstration in healthy volunteers that EP is safe,
tolerable, and effective in improving the magnitude, breadth and durability
of cellular immune responses to a DNA vaccine candidate.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00545987","term_id":"NCT00545987"}}NCT00545987 |