A monovalent influenza DNA vaccine delivered by a Particle Medicated Epidermal Delivery (PMED) needle-free injection system has been shown to be safe in Phase I trials.
The trial examined three doses (1, 2 and 4mg) of a DNA plasmid encoding the H3 haemagglutinin (HA) gene for Panama flu. When administered in a 4mg dose all 36 volunteers on the trial achieved a "seroprotective level of antibodies" and passed the Committee for Proprietary Medicinal Products' (CPMP) criteria for immune response at 21 days. All three doses, (1, 2 and 4mg) passed the CPMP criteria at 56 days.
The vaccine, developed by PowderMed (Oxford, UK), was well tolerated and will now enter Phase II studies using both annual and bird flu strains later this year.
"Recent years have seen a number of new influenza vaccine approaches tested in animal model systems and in the clinic," said Dr. Hansi Dean of the International AIDS Vaccine Initiative. "However, this study is the first successful demonstration of immunogenicity of an influenza DNA vaccine in humans.The relative immunogenicity of PowderMed's DNA vaccine compared to intramuscular DNA vaccination is likely attributable to the efficiency of intracellular DNA delivery by PMED."
The PMED device is a single-use, disposable device powered by high-pressure helium stored in a self-contained micro-cylinder. The DNA plasmid that forms the active component of the therapeutic vaccine is precipitated onto microscopic gold particles that are used as the plasmid DNA carrier. These microscopic particles appear as a stable dry powder which is then filled into sealed cassettes that act as the primary drug product container and are inserted into the PMED device during the final product assembly and packaging process.
The device is used by placing the nozzle against the skin at the delivery site and pressing the actuation button. This releases the helium which ruptures the cassette membrane and thus propels the particles from their stationary state in the cassette through the nozzle and towards the skin surface at high velocity, where they reach the target epidermal cells.
DNA immunotherapy delivers the DNA into the nuclei of cells and thereby elicits an immune response much more efficiently than through direct injection, which delivers the DNA to extracellular spaces and relies on non-specific and relatively low natural uptake of the DNA by neighbouring cells or transport along lymphatic vessels to draining lymph nodes.
PMED delivery thus uses 1,000-fold less DNA than needle and injection administration and consequently comes at a lower cost. This vaccine's stability at ambient temperature and the fact that the cassette is sealed mean that PMED can also be stored simply and cheaply.