OHSU scientists look for methods to improve vaccinations for smallpox and other infectious diseases

May 19, 2003

PORTLAND, Ore. - Oregon Health & Science University (OHSU) researchers are studying new methods to dramatically increase the number of people who can receive vaccinations against smallpox and other deadly diseases. Currently a significant segment of the U.S. population cannot receive these vaccines because their immune systems are weakened. This condition, called immunosuppression, can be found in many groups, including 30 million to 40 million elderly people in the United States, those battling anxiety or depression, AIDS and cancer patients, and stroke survivors. Such immunosuppressed individuals are often referred to as "vulnerable" populations because they are especially susceptible to infection.

"One of the vulnerable groups that cannot be vaccinated with certain vaccines are those who take steroids," said Mary Stenzel-Poore, Ph.D., associate professor of molecular microbiology and immunology in the OHSU School of Medicine. "Steroids can also cause immunosuppression. Currently 25 million to 30 million people are taking steroids for various health conditions. That's an extremely large segment of the population at great risk of powerful emerging infectious diseases, such as SARS, or in the case of bioterrorism."

Many vaccines work through purposely infecting the patient with a mild, related form of the disease. For example, in the case of smallpox, the virus vaccinia is the active ingredient. The related virus causes the body to produce protective antibodies and specialized white blood cells, called T-cells, that can search for and destroy cells infected with the more serious form of the disease (i.e., smallpox itself).

In most patients, vaccines result in little to no illness whatsoever. However, patients with compromised immune systems may face serious illness or death because their bodies can't fight off the infection caused by the vaccine. Even when inoculated with those vaccines that cause no infection, many patients who belong to vulnerable populations fail to generate a sufficiently strong immune response to fight the real infection.

To look for methods to treat these patients, researchers at OHSU will use animal models that mimic human immunosuppression. These animal models allow researchers to study the impact of infectious diseases in immunosuppressed individuals and figure out ways to increase protection. Using these models, scientists will investigate causes behind vulnerability of the immune system, as well as new vaccine types and delivery methods.

"For example, splitting the normal dose of vaccine into several smaller doses may result in disease protection without endangering the life of the patient," said Janko Nikolich-Zugich, M.D., Ph.D., senior scientist at the OHSU Vaccine and Gene Therapy Institute. "We're also investigating whether new types of vaccine delivery may boost immunity while reducing dangerous infections. For instance, injecting a modified vaccine or injecting at a different location of the body may be a solution. Finally, we're looking into combination drugs, compounds that can act as a booster for the immune system, so vaccinations do not have adverse health effects on immunosuppressed patients."

This research will be conducted in conjunction with other institutions in the Pacific Rim Biodefense Center (PRBC). The PRBC is a collaborative effort headed by OHSU. Member institutions will investigate new ways to fight infectious diseases spread through natural causes or bioterrorism that threaten human health. The PRBC includes the University of Hawaii at Manoa; the University of Nevada, Reno; Oregon State University; the University of Idaho; Princeton University; and Pacific Northwest National Laboratory (PNNL).

In addition to the PRBC, OHSU has proposed expansion of research and facilities aimed at developing vaccines to combat infectious disease. More information about this effort, called the Pacific Rim Vaccine Initiative, can be found at www.ohsu.edu/prvi.
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Oregon Health & Science University

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