LANGEN, Germany - More than 20 scientists from the U.S., Canada, and Europe discussed the development and clinical progress of DNA vaccines during a three-day conference held here at the German Federal Agency for Sera and Vaccines (Paul-Ehrlich Institute, PEI).

During the conference details of the forthcoming "European Note for Guidance" on DNA vaccines were announced.

"Since the first demonstration of the proof of principle of DNA vaccines in animal studies back in 1993, the field has progressed really fast," Reinhard Kurth, president of the PEI, said. "The aim of the conference is to discuss new developments as well as regulatory aspects, safety and efficiency of DNA vaccines."

The PEI is responsible for the licensing and batch control of biological drugs for both human and veterinary uses and is entitled to issue directives to pharmaceutical companies and blood transfusion centers. In addition, the institute carries out research programs, especially in AIDS and gene therapy.

DNA vaccines do not contain an inactivated or live infectious agent but pieces of its DNA. When this DNA is translated in the body of the recipient, the resulting protein induces a strong immune response. As animal studies with DNA vaccines against viral, bacterial, and parasitic diseases produced favorable results, 12 human clinical trials were started during the last years, most of them in the U.S.

Currently, DNA vaccines against malaria and HIV, hepatitis B, herpes simplex and influenza viruses are being tested in humans. So far, none of the studies has progressed into Phase III.

Achievements and problems of the field were summarized by Stephen A. Johnston, one of the inventors of DNA vaccination. He said he and his colleague, John Sanford, had viewed genetic immunization both as a simpler and possibly better way of administering vaccines and as a means to facilitate discovery about how the immune system worked and of new reagents for vaccines. In spite of impressive preclinical reports, however, animal and human clinical trials had given mixed results, he said.

"I think it is clear," Johnston said, "that there are three important limitations to address: One is delivery to the right cells. In spite of a misguided emphasis on muscle initially, it is now clear that genetic vaccines should be directed to antigen-presenting cells, particularly dendritic cells. Targeting strategies should be developed. The second is that devices for delivery are inadequate, particularly for large animals." Needle injection was archaic and would deliver to the wrong cell bed, he added. The gene gun could deliver to the right area but precluded targeting. "Third, we need to rethink how we identify a good vaccine."

Klaus Cichutek, head of PEI's Department of Medical Biotechnology, and James Robertson, member of the Biotechnology Working Party of the European Central Committee for Proprietary Medicinal Products (CPMP), told the conference about the development of a "European Note for Guidance" on DNA vaccines currently under development by the CPMP. The note will include guidance for the preparation of plasmid DNA for both gene therapy and vaccination. The information will not be restricted to quality aspects but also will include guidance information on preclinical safety evaluation, clinical efficacy and safety, and on considerations on the use of genetically modified microorganisms.

Currently to initiate clinical trials in some member states a positive opinion of a local and a central ethics committee is necessary, and approval of a competent authority has to be obtained. In other countries notification of competent authorities is sufficient. Cichutek said the European Note for Guidance would provide a "one-door, one-key approach" in the future.

"In order to obtain marketing authorization for DNA vaccines in all European member states, only a single application at the European Agency for the Evaluation of Medicinal Products will be necessary in the future," Cichutek said. "This will allow rapid access to the European drug market."

According to the draft, an early notification of the EMEA and the establishment of a database comprising relevant clinical trial data will foster communication between member states and mutual recognition of clinical trial approval.