LONDON -- Drug delivery company Powderject Pharmaceuticals plc has reached a key milestone in the development of DNA vaccines with the announcement that its hepatitis B vaccine is the first to elicit a protective response in humans. Interim analysis of 11 subjects in the Phase Ib clinical trial showed they had all seroconverted to antibody levels that are accepted as conferring protection against hepatitis B. The trial, conducted by partner Glaxo Wellcome plc, of London, triggered a $1 million milestone payment to the company's wholly owned U.S. subsidiary, Powderject Vaccines Inc., of Madison, Wis.

Paul Drayson, Powderject's chairman and CEO, told BioWorld International the finding "is an extremely significant achievement for Powderject and Glaxo Wellcome. It is also very important for DNA vaccines generally, because we have shown that they work in humans. While there has previously been encouraging animal data, animals are not good models of the human immune system."

The trial enrolled 12 subjects and was designed to test the safety of the vaccine and measure the immune response elicited by ascending dosages. Each subject received a prime and two boosts of DNA vaccine encoding the surface antigen of the hepatitis B virus. The product is formulated as a dry powder and delivered through the skin, using Powderject's needle-free delivery system. The interim analysis of the eleven subjects who have completed the schedule so far showed they had all seroconverted to a protective antibody level of 10 milli-international units per milliliter or higher, and that the vaccine was well tolerated. The subjects will be followed for up to 18 months.

A prophylactic vaccine for hepatitis B is one of 11 DNA vaccine fields covered by Powderject's agreement with Glaxo, signed in March 1998. This would be a significant product, with sales of the current vaccine standing at $1 billion per year. Further development is under way to optimize vaccine performance, including possible vector modifications, changes to the dose and vaccination schedule and improvements to the delivery system. "We want to make it clear that we are developing a technology platform, working not just on hepatitis B but a whole series of indications," said Drayson.

"The payment of the $1 million milestone payment shows the hepatitis B vaccine is effective," he added. "It also speaks to the effectiveness of our delivery system, which is intrinsic to achieving the immune response, and shows that we are developing a broad platform in DNA vaccines."

Powderject, based in Oxford, has developed a powder formulation for DNA vaccines in which DNA is adhered to microscopic gold particles. The dry powder is administered by the company's hand-held, needle-free system, which uses a burst of helium gas to accelerate the particles through the skin. Once inside the epidermal skin cells, the DNA separates from the gold particles and produces immunogenic compounds. The company says the system can be used for traditional vaccines, and could also be applied to immunotherapy for cancer and/or immune disorders.

Drayson noted that the system delivers the vaccine intracellularly.

"Our competitors using a needle and syringe are in effect depositing a pool of DNA outside the cell," he said. "Our system delivers the DNA directly to the cell, where it is processed in a way that mimics what happens when a cell deals with an infection." This means that far less DNA is needed to elicit an immune response. Drayson said the delivery technology could be applied to gene therapy in general. The deal with Glaxo includes developing the technology for cancer.

Last week, Powderject said it had been awarded a European patent on the technology for delivering microparticle DNA vaccines using its needle-free system. The patent, which is licensed to Powderject exclusively for all mammalian applications, covers intracellular delivery of any biologically active particle.

"This patent strengthens our leadership position in particle-mediated DNA vaccination and represents a pivotal patent for us in Europe," Drayson said. *