STIMULATING BOTH ARMS OF THE IMMUNE SYSTEM

In late April, ViRexx Medical, for which Dr. Tyrrell serves as the Chief Executive, received authorization from Health Canada, the country's regulatory arm which is similar in nature to the U.S. Food and Drug Administration, to undertake a Phase I clinical trial for its lead Chimigen platform vaccine candidate, HepaVaxx B. Dr. Tyrrell hopes it might become a potential treatment for chronic carriers of the hepatitis B virus. Tyrrell told StockInterview, "The platform is designed to try to get both a T and B cell response. Most conventional vaccines induce just a B cell response."?

It is the dendritic cells, which stimulate the B-Lymphocytes and produce antibodies. For example, the mumps vaccine was designed to give a B cell response, providing someone with good protection for a number of years. As Dr. Rajan George had told us, "The B-Cells produce antibodies against the virus antigen, which we have put in the Chimigen vaccine. The antibodies are specific to the antigen and bind to the viruses because they have the antigen. The system removes the virus by binding with the antibody."? The platform is also expected to remove the infected cells using cytotoxic T-lymphocytes.

The big breakthrough in treating many infectious, and other, diseases would come with the vaccine platform capable of stimulating both a T and B cell response. "It would be a major step forward,"? Tyrrell noted, "if we could find a way to increase the efficiency of some of these therapeutic vaccines."? ViRexx Medical's infectious disease department conducted a number of ex vivo laboratory experiments to evaluate the immune responses the Chimigen platform might produce. "We showed what we had predicted in theory has been true,"? Dr. George told us. "We have also done some animal experiments, where the vaccine showed similar effects, again, as predicted. For HepaVaxx B, the animal results are also showing great progress and promise."? Tyrrell is more reserved in his expectations, "Let's see how the platform works when tested in humans. If this can be used to stimulate both a T and B cell response, then it would be a significant breakthrough."?

There could be stumbling blocks ahead. A chronic hepatitis B carrier is exposed to a number of antigens in his or her body. Tyrrell has further concerns which may arise. Perhaps the antigen might not trigger a strong enough response. Or something may be discovered during the Phase I trials, such as "Are there regulatory T cells, or cells that are being paralyzed and not being allowed to stimulate a strong immune response in these patients? That is why one tests in humans after successful animal tests, to address those points of interest. As Dr. George reminded us, "Until then, our optimism is based on laboratory results."?

Tyrrell has already begun thinking a few steps into the future, "I really believe we've found a way of directing the right immune response chimigens, but we may have to use adjuvants to get a strong immune response."? Adjuvants are immunological agents designed to induce the production of antibodies. "We haven't used the platform with an adjuvant to get an even stronger response,"? explained Tyrrell. For example, nucleotidesis, the short nucleotide sequences which are rich in CpG, or growth factors, such as cytokines, can enhance the immune response.

DEVELOPING A CLASS OF FLEXIBLE VACCINES?

Ever the optimist, Tyrrell outlined his strategy, "Our plan is to go with one or two antigens first and see that we get the appropriate immune response. If we do, then we will be looking at other antigens, not only from viruses, but we can be looking at cancer antigens in this platform."? Dr. George echoed Tyrrell's sentiment, "We should be able to use this platform for cancer therapy, depending upon the cancer antigen we use. We can plug in a specific cancer antigen into this platform, and the vaccine targeted to dendritic cells."? The company has also been evaluating some bioterrorist viruses in conjunction with an arm of Canada's Defense Department. Dr. George also pointed out, "Our chimigen technology is not found anywhere outside of our laboratories. This approach has not been tried before for chronic HBV or HCV infections."? Because the scientists believe the Chimigen platform is one which may be flexible and adaptable for the treatment of both infectious viruses and cancers, a new class of vaccines may be developed over the coming decade.

While awaiting the results of the initial human clinical trials, Dr. Tyrrell did reach a very definite conclusion about the mission in his journey, "Unless you have both arms of the immune system, you may not have lifelong immunity."? Tyrrell's down-to-earth thinking may have come from being born on a farm in rural Alberta, west of Edmonton, the big city where his college alma mater can be found. At one time, he had considered becoming a rural family physician or a veterinarian. His erstwhile aspiration to work with animals is ironic, because his research has involved virally infected duck models, chimps who love the taste of Tang, and mouse antibodies. But Tyrrell's curiosity to solve complex scientific riddles has taken him beyond those once-simple goals.

His competitive drive for milestones was first evidenced by winning a gold medal in science, while an undergraduate majoring in chemistry at the University of Alberta. An then, with an award of a New York Life insurance scholarship, during his second year in medical school, for a combined MD/PhD. Only twenty-two medical students in North American won such a scholarship that year. Or perhaps he hoped where his journey might someday take him, when he won an MRC Centennial fellowship to study virology, for two years, at the Karolinska Institute in Stockholm. For those unfamiliar with this Swedish institute, it is the home of the Nobel Prize. Is this where Dr. Lorne Tyrrell's journey might one day reach its final destination? The answer to this question may come from the results of the clinical trials for his Chimigen platform.