Issue



Bio techniques: shooting tiny gold bullets at viruses


11/01/2006







By John Carroll

Researchers at U.K.-based PowderMed say they’ve scored a bull’s eye with a new gene gun. Their early clinical data demonstrates that microscopic-sized particles coated with genes extracted from specific flu strains and blasted into the skin at supersonic speeds offer a needle-free approach to vaccinations. And they’ve been developing a new program for avian flu that they believe can duplicate the results of an earlier trial that registered an immune response in every volunteer that took part in the small study.

PowderMed’s DNA vaccines take part of a flu strain and tattoo it into the epidermal layer of the skin, a process that allows the vaccine to penetrate the cells in the skin’s immune network. By using the protein encoded in the flu strain, either the annual variety or the H5N1 bird flu strain, the researchers say they can spark an immune response that would direct a body to attack any such virus that attempted to invade the host.

PowderMed’s work fits into a broader movement in the vaccine field to move away from egg-based vaccines, which can be notoriously slow to manufacture and are constantly threatened by contamination. These new vaccines also don’t need to be refrigerated - a big plus when vaccinating third world populations - and can be easily administered. The approach could also provide immediate protection even after a mutation changes the avian flu virus, a process known as drift.

“Firstly, we have shown that our DNA technology has the potential to provide good protection against historical drift variants of both annual flu and H5,” says John Beadle, PowderMed’s chief medical officer. “We are currently doing some further work to demonstrate cross protection with recent H5 variants. Secondly, it is much quicker and simpler to insert a new H5 segment into a DNA vaccine than it is for an egg or cell-based vaccine. For this reason, our DNA technology will be able to closely track the evolution of a pandemic.”


On actuation, the release of helium from a self-contained micro-cylinder ruptures the cassette membrane and propels the particles from their stationary state in the cassette through the nozzle and toward the skin surface at high velocity. This results in the deposition of the microscopic DNA coated gold particles in the epidermal cells of the skin. Images courtesy of PowderMed
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The data backing the effectiveness of DNA-based vaccines dates back to the early ’90s, says Beadle. But that work hit a scientific brick wall when researchers tried to immunize humans or big primates. Small science, he says, has given PowderMed a chance to overcome that big hurdle. By coating a gold particle the size of one to three microns and impregnating it into the skin, researchers are able to deliver the vaccine right into the nucleus of the cell, sparking the immune response that was lacking in earlier efforts.

PowderMed now has three early-stage clinical trials underway in the U.S. and the U.K. In late May, researchers for PowderMed reported that all 36 volunteers involved in a Phase I trial of its program for seasonal flu recorded a protective response to the maximum dose of its vaccine.

In most cases involving the development of a new therapy, researchers in Phase I could expect to spend many long years planning more advanced clinical trials. But with avian flu driving the process, the company says it expects to pursue regulatory approval at a much faster pace. Initial safety and efficacy data from the first human trials should be available in the early part of next year. And from there they can go straight into Phase II with a concurrent Phase III that runs through the ’07/’08 flu season. FDA and European regulators could have data to consider in 2008, which would put this particular program on a fast track rarely seen in biotechnology.

In the event a bird flu pandemic actually breaks out among humans, says Beadle, that timetable could also be significantly accelerated. In the meantime, PowderMed also hopes to make its mark in other therapeutic areas outside of influenza.

“The exciting point about our DNA vaccines is that they induce cellular immunity as well as humoral immunity,” says Beadle. “Cellular immunity can be directed to eliminate chronically infected cells, as in HIV/AIDS, or malignant cells, as in many types of cancer.”