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LIAI initiatives battle influenza; Potential bird flu treatment among their findings


The La Jolla Institute for Allergy & Immunology (LIAI) is making significant strides in the battle against the avian "bird" flu, with pre-clinical trials under way on a potential treatment conceived by one of its scientists. The Institute, a not-for-profit organization whose cutting-edge research focuses on infectious diseases and other immune system disorders, is also developing information for a "universal" flu vaccine, as well as researching a needle-free vaccine that would treat various influenza strains, including the avian flu.

The Institute, which launched an Emerging Infectious Disease and Biodefense Research Center in 2004, is conducting three major research initiatives to attack the influenza virus -- all of which may be applicable to the avian flu strain, known as the H5N1 virus. "We understand the devastating potential of an avian flu outbreak as well as the problems caused each year by the more conventional flu strains," said Mitchell Kronenberg, LIAI President and Scientific Director, noting that 200,000 Americans are hospitalized and 36,000 die each year from the flu. "Our researchers are working diligently to understand the cellular mechanisms that hold the key to preventing or treating influenza," he said. "We are particularly excited that our research shows promise against the avian flu, as that may be the most urgent health issue now facing the world."

A potential treatment for the avian flu involving human flu-fighting antibodies was conceived by LIAI scientist Hilde Cheroutre, Ph.D., and initiated through a collaborative effort of LIAI and Gemini Science, a biopharmaceutical research and development company and wholly-owned U.S. subsidiary of Kirin Brewery Co., Ltd. of Japan. Gemini moved forward in 2000 with laboratory testing on the antibodies, which have produced preliminary data showing positive results against numerous flu strains, including the H5N1 avian flu.

Cheroutre’s concept focused on M2, a protein common to all influenza A viruses, including avian flu strains. Her insight was to suggest using a portion of the M2 protein to immunize Transchromosomic miceTM, which are mice genetically-engineered to produce human antibodies. The TC MouseTM Technology, developed by Kirin’s Pharmaceutical Division, allowed researchers to obtain influenza M2-specific human antibodies.

In conducting the research, Gemini scientists used synthetically created pieces of the H5NI avian flu virus, along with a number of other synthesized virus pieces, to analyze the effectiveness of the human anti-M2 antibodies, which had been created from theTranschromosomic miceTM. "In laboratory (in vitro) testing, they found that the anti-M2 antibodies bound to several different influenza strains, including the avian flu virus (H5N1)," Cheroutre said. "This reactivity means that if used in vivo (in a living organism) the infected cells would be recognized by the antibody and destroyed by the immune system." The study also found that a relatively low dose of the antibodies was needed to fight the various flu strains.

While most of the work was done on virus pieces to avoid the risk of using actual viruses, Gemini also tested the M2 antibodies on mice infected with a potentially lethal influenza strain, with similarities to the avian flu virus. "They found that those mice which received the human M2 antibody were protected, while those mice that did not get the M2 antibody would die," Cheroutre said.

Based upon the lab and mice testing, Gemini Science is now initiating pre-clinical studies required for the commencement of human clinical testing of the anti-M2 antibody, said Shinichiro Kato, Ph.D., Gemini’s Chief Scientific Officer. Gemini, which is testing the antibody both as a treatment and preventative measure against flu, has expedited the research due to the recent cases of avian flu. Gemini is currently in discussions with the Centers for Disease Control (CDC) about establishing a Cooperative Research and Development Agreement to jointly conduct further research. Gemini’s findings were presented Saturday at the 45th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), which runs through Monday in Washington, D.C.

LIAI scientists are also engaged in other promising flu-related research, including work by scientist David Lo, M.D., Ph.D. Together with Neurome, Inc. in San Diego, Lo recently received a $3.9 million Bill and Melinda Gates Foundation Grand Challenges in Global Health grant to work on a mucosal flu vaccine that could be given orally or nasally. This needle-free vaccine delivery system would enable vaccines to be administered in any field setting without the need for complex equipment or specialized training. This would be particularly helpful for improving health in third world countries, which is the focus of the Gates grant. Along with a novel delivery system, if successful Lo’s research would produce the world’s first targeted mucosal flu vaccine, which would bind to specific receptors in mucosal surfaces such as airways and intestine. It is believed that such a vaccine would produce more rapid, potent and longer lasting flu protection than today’s vaccines, because it would attack the virus in the mucosal linings where it enters the body. Lo said the vaccine would be designed to fight numerous flu strains, including the H5N1 avian flu.

LIAI’s other major area of flu research involves studies that could lead to the development of a "universal" flu vaccine, meaning one that would protect against a broad cross section of flu viruses.

LIAI scientist Dr. Alessandro Sette, Ph.D., a renowned vaccine expert, is using powerful biomedical research tools to measure the immune response of people who have previously had the flu. His work involves comparing the various immune system reactions of test subjects against the genetic sequence of the vaccine virus.

"We are interested in seeing whether there are different components or pieces of the flu virus that are recognized by the immune system," he said, explaining this would mean the immune system had seen those pieces previously in earlier flu exposures. "Specifically, we’re looking to see if there are proteins or genes that are common to many flu viruses that are targets of the immune response. If so, it may be possible to develop a vaccine with greater cross protection because it would recognize elements common to all flu viruses."

Bonnie Ward | EurekAlert!
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