Lean mean gene vaccine
April 26 2002, The Washington Times
Finnish biotech company FIT Biotech starts human trials
of a DNA-based HIV vaccine
Two decades after the discovery of HIV, the search is still on for a cure and preventive medicines. A lot has been discovered about the immune system since then and drugs are prolonging patients´ lives by up to two decades, but there is still no vaccine. Traditional ways of producing vaccines have proven unsuccessful at preventing HIV/AIDS. A company in Finland, FIT Biotech, believes scientists must move away from traditional thinking. The company started human trials of a DNA-based HIV vaccines this past December.
Vaccines are generally the most cost-efficient way to prevent infectious diseases. Treatment with the drugs available on the market today runs from $2000 to $8000 per drug per patient per year. Vaccination costs could be as low as $20 per patient. Developing a vaccine for HIV has been tricky however, for several reasons.
There have been two or three generations of vaccines. The traditional vaccines are produced mainly two different ways. Attenuated vaccines, or live vaccines, carry mutations of the vaccine. They do not cause a disease but raise immune response. Measles and smallpox vaccines are examples of live vaccines. This method is not applicable to the HIV virus, as attenuated HIV vaccines have been shown to become virulent in lab tests. The second type of vaccines, inactivated vaccines, consist of whole microbes that have been killed by heat or chemicals, or more simply, are part of the microbe that provokes the immune system to respond. The Hepatitits B vaccine is an example. Unlike live vaccines, inactivated vaccines cannot replicate and so cannot cause even mild cases of the disease, but their presence still prompts the immune system to respond. For HIV prevention however, inactive vaccines have been proven ineffective. The answer, FIT Biotech believes, is a gene-based vaccine, using technology such as FIT Biotech´s Gene Transport Unit.
FIT Biotech´s idea is to inject DNA plasmid directly into the body, either into a muscle or into the skin. The DNA plasmid encodes the desired foreign antigen, in other words the virus, and forces the body to produce an immune response against the virus. In contrast to traditional vaccines that contain the antigenic material itself, DNA vaccines provide host cells with the genetic code for the intracellular synthesis of the immunizing antigens. To put it simply, DNA vaccines give the cells the genetic answers for how to protect themselves. The DNA vaccine mimics a natural infection as it encodes the antigenic material that is then synthesized in the host cell, but since no virus is used in the vaccine, it cannot cause infection. "It mimics the real virus, but in a safe way," President of FIT Biotech Dr. Pekka Sillanaukee says. DNA vaccines are not problem-free however. "Most people believe DNA-based vaccines are the future. But there have been problems to generate strong and long-term immune reponse with these vaccines. We believe that the Gene Transport Unit overcomes these limitations," Sillanaukee says.
The world needs a vaccine. The HIV drugs developed in the nineties prolong HIV patients´ lives by an average of ten years, and in best cases up to twenty years. Costs, however, put these drugs out of reach for people in countries where they are needed most. In industrialized nations, side effects and viral resistance have been caused concerns about the drugs´ long-term use.
There are over 35 million people living with HIV/AIDS worldwide and 5.8 million people are infected yearly. Over twelve million children have lost one or both parents to AIDS. Finland has a relatively small number of HIV-infected inhabitants. Information and preventive methods, such as distribution of condoms and clean syringes, has led to one of the lowest HIV statistics in Europe. Since the virus´ discovery in the mid-eighties, about 1300 people have contracted HIV in Finland. Of these, about 340 have developed AIDS, and about 250 have died. Similarly, in Europe prevention programs have slowed the spread of HIV, but have not stopped it. Only an HIV/AIDS vaccine can end the pandemic.
A vaccine goes through several phases after its initial discovery before it is ready for commercial use. The discovery and research phases are followed by pre-clinical and clinical trials. Clinical trials are divided into Phase I, II and III. FIT Biotech just entered Phase I clinical trials. Twenty Finnish HIV-infected volunteers are participating in the program, carried out in cooperation with the Department of Dermatology and Venereology at the Helsinki University Central Hospital. "It will take about a year until we see the results," Sillanaukee says. "If all goes nicely, we might see a vaccine by 2007 to 2011, but a more realistic time frame is 2010 to 2015." Phase III requires a lot of money and multi-site trials around the world. Sillanaukee hopes the initial phase of the clinical trials will show enough promise to move on to phase II studies and attract international investors.
HIV research in Finland dates back almost as far as the discovery of the virus. FIT Biotech´s Dr. Kai Krohn and Dr. Annamari Ranki started HIV research in 1983 and HIV vaccine research four years later. The DNA-based HIV vaccine studies have been going on for almost ten years.
FIT Biotech was started with seed money from public funds and investments from five private Finnish investors. SITRA, The Finnish National Fund for Research and Development, is still the biggest owner. Biotech investments are generally high risk, and the return on investments might not be visible for a decade, maybe two. "Biotech is a fresh, new field. For new areas it is always a little more difficult to get funding. We need very specialized investors who understand the field and that it may take a relatively long time before they see the returns. For us, it is very important to have institutions like Tekes and SITRA that are willing to invest in high-risk areas. They see the possibilities."
There are different variations, or glades, of HIV. Glade A dominates the African continent, where the virus originated. Glade B is most common in Europe and North America and in Asia, where the virus is spreading most rapidly. Glade C is the most prevalent. FIT Biotech´s research focuses on finding a vaccine for the Glade B virus. Is this because that´s where the funding is, and there is less interest from investors to find a vaccine for the world´s hardest hit areas? "No, we started with Glade B because of practical reasons. It was natural to start with B because we had European support. A vaccine should either be focused on one glade, or be cross-glade. We have started on the B glade, but our aim is to cover the major glades of HIV. It´s rather easy to repeat the results with other glades."
With new ideas and novel technologies, FIT Biotech believes it is getting closer to stopping the pandemic.
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