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USF research shows promise for asthma vaccine
By WES ALLISON © St. Petersburg Times, published February 11, 2001 TAMPA -- In a sprawling lab just down the hall from his office, Dr. Shyam S. Mohapatra and his team tweak tiny genes in hopes of making big changes. With asthma cases spiking since 1980 and no end in sight, many researchers believe their best chance for stemming the disease is a vaccine based on gene therapy. Asthma and allergies are caused by immune system disorders. At the University of South Florida in Tampa, Mohapatra and other researchers are trying to devise a vaccine that would force the body's immune system to cope properly when faced with allergens or respiratory infections.
A marketable human vaccine is probably five to 10 years away, but USF researchers have successfully used a vaccine in mice to stop lung inflammation from an illness called respiratory syncytial virus, or RSV. RSV mimics asthma in the lungs and can cause asthma to develop over time in some people. Photos from a national research article the USF team published attest to the outstanding difference: In the untreated mouse, the airways of the lungs are nearly swollen shut. In the treated mouse, they are clear. The same concept should work for people, too. "We think it can be very effective for children who are going to develop allergies and asthma, and it may work for people who already have allergies and asthma," said Mohapatra, a professor of medical microbiology and immunology and director of basic research at the Joy McCann Culverhouse Airway Disease Center at USF. Asthma is a complex disease that can be caused by mutations of many genes, but researchers believe just a few are responsible in the early stages. At USF, scientists are searching for those genes by comparing the genes of asthmatics with the genes of other people. It is tedious and time-consuming. They also are focusing on one apparent culprit, an immune system gene that thwarts the production of interferon, a key immune cell. When the body doesn't make enough interferon, the immune system overcompensates. Through a series of steps, it produces an excess of an antibody called IgE. IgE is found in large quantities in the lungs of asthmatics and apparently contributes to the inflammation caused by asthma and RSV. Stop the overproduction of IgE, some researchers believe, and they will ease the asthma. Future asthmatics could be identified through genetic testing and treated in infancy with a vaccine. "The best way to treat asthma is to prevent it, like hypertension or diabetes," said Dr. Richard F. Lockey, director of USF's division of allergy and immunology. "Most people chase it: attack, then treat, attack, then treat." Asthmatics can expect to hear more about IgE in the near future. Genentech Inc., a California biotech firm, and pharmaceutical giant Novartis hope to win federal approval this summer for a drug called Xolair, designed to treat asthma and seasonal allergies by reducing levels of IgE. Last year, the company reported that results from its clinical trials were promising. "It's very different because other therapies often target symptoms," spokeswoman Wendy Emanuel said. "Xolair is designed to act much earlier in the chain of allergic events." Any effective treatment could be a gold mine: Sales of asthma-related prescription medications surpassed $6-billion last year, a 17 percent increase over the year before, according to IMS Health, which tracks prescription sales. Asthmatics and their doctors rely on a large stable of highly effective daily and emergency medications. Most people with moderate or severe asthma take an inhaled steroid once or twice a day to reduce the underlying inflammation of their lungs, then use a fast-acting inhaler, such as albuterol, to ease attacks. Because these work so well, pharmaceutical firms are seeking easier ways for people to take them, which they hope will make their drugs more appealing, said Alisa Diecidue, administrator of the Asthma, Allergy and Immunology Clinical Research Unit at USF, which tests asthma medications. "They want the best delivery system with the least side effects. They want the most convenience," she said. "If your child has asthma, it's easier to take a pill . . . than to use an inhaler." The newest drugs on the market are leukotriene inhibitors, such as Singular and Accolate, that ease inflammation by blocking a step in the asthma process. They're designed as alternatives to steroids and are taken by pill, and they are proving popular: Use more than doubled last year, to $791-million in sales.
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