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College Researcher Receives $1.8 Million Grant to Study Better Vaccines

Albany, N.Y., November 5, 2007-Dennis Metzger, Ph.D., professor, Theobald Smith Alumni Chair and director, Center for Immunology and Microbial Disease at Albany Medical College, has received a $1.8 million, 5-year research grant from the National Institutes of Health, National Institute of Allergy and Infectious Diseases for continued support of his vaccine research. Dr. Metzger has been researching more effective approaches for vaccination against bacterial and viral diseases. Specifically, he has been studying how to make safe, inhaled or oral vaccines that target areas where diseases enter the body.

Dr. Metzger explains that most vaccines are administered as shots-they enter the bloodstream directly and we build an immune response against the disease the vaccine is aimed at preventing. While this can work very well, a major drawback of injected vaccines, he says, is that they don't always produce a good immune response in the mucous membranes (the respiratory tract, gastro-intestinal tract and genitourinary tract) where viruses and bacteria first enter the body.

"Gaining protection in this mucosal tissue is really the first line of defense," says Dr. Metzger. "Therefore, vaccines that can be swallowed or inhaled are going to work better than those that enter the body through the bloodstream." While injected vaccines work for the majority of people, success rates can be 70, 80 or 90 percent, meaning a significant number of individuals (up to 20 or 30 percent in some cases) do not get protected. Vaccines that target the mucosal tissue can have success rates of close to 100 percent.

A good example is the oral polio vaccine. A drop of vaccine is swallowed and enters the gastro-intestinal tract (the same place where polio enters) and immunity develops there, making it an extremely effective vaccine responsible for eradicating the disease in this country, according to Metzger.

The catch is that currently available oral and inhaled vaccines, like the oral polio vaccine, are made up of "live" bacteria or virus that has been weakened to promote an immune response without causing full-blown disease. (Most injected vaccines, on the other hand, like the injected polio vaccine, are not "live," but "killed" or "inactivated"-made up of just a small portion of a virus or bacteria that is incapable of causing disease but that can still cause the body to build an immune response.)

"So live virus vaccines work really well, but sometimes they can cause the disease they are trying to prevent, or have other side effects in certain groups of people," says Metzger, pointing out that people with compromised immune systems might not be able to mount a good immune response even against a weakened virus. "That's why we don't use the oral live polio vaccine in this country anymore," he says. "It's more effective, but since we don't have polio around, we can get away with using the less effective 'killed' injected vaccine."

The ideal vaccine, Metzger maintains, would be a 'killed' oral or inhaled one-a vaccine that targets the mucosal membranes directly but doesn't carry the risks of a live virus vaccine. The NIH grant supports his work to investigate the feasibility of such a vaccine. Specifically, he's studying how it could be administered.

"When we use a killed virus or just a portion of a virus to make a vaccine, we need to have another ingredient in there as well, one that will help us build an immune response. Most injected vaccines use an aluminum salt as an aggregate to boost immunity. But, aluminum salt can't be used in an inhaled or oral vaccine, so we need to find something else," says Metzger. The compound he?s been studying as a possible immune booster is called Interleukin 12 (IL-12), a natural substance produced by the body's immune system, which appears to activate the immune system to fight disease.

"In animal studies, we've found that IL-12 can produce protective immunity in the respiratory tract. So, we're continuing to study it with various bacteria and viruses to see if it can be protective. We think that IL-12, or something like it, could be used at some point in the creation of new vaccines," says Metzger.

A challenge he faces, Metzger says, is that while we know a lot about how the immune system functions in the bloodstream, we don't know how the immune system in the lung functions. "If we can understand more about the pulmonary immune system, we can use that knowledge to our advantage to make better inhaled vaccines against diseases that target the lung."

This research has been continually funded by the NIH since Metzger joined the faculty in 1999.

Albany Medical Center is northeastern New York's only academic health sciences center. It consists of Albany Medical College, Albany Medical Center Hospital and the Albany Medical Center Foundation, Inc. Additional information about Albany Medical Center can be found at www.amc.edu.