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Building better therapeutic vaccines for chronic infections

PHILADELPHIA - In recent years, researchers have become increasingly interested in developing therapeutic vaccines. Most Americans are familiar with prophylactic, or preventive vaccines, which protect an individual from infections; examples include the common pediatric vaccines as well as the flu shot. But therapeutic vaccines are designed instead to be administered to patients who have already acquired chronic infections, such as HIV or hepatitis. These therapeutic vaccines aim to enhance the immune system's ability to combat an infectious agent, such as a virus. Researchers are also developing therapeutic vaccines to treat a variety of cancers.

But many experimental therapeutic vaccines have thus far fallen short of expectations. Now, scientists at The Wistar Institute and Emory University offer details about what may prevent the immune system from responding effectively to a therapeutic vaccine during a state of chronic infection. Their findings suggest how scientists might alter therapeutic vaccination approaches to make the immune system respond better. Their work is published today in the Journal of Virology.

"In this study, we wanted to look at why therapeutic vaccines are generally less effective than prophylactic vaccines," says E. John Wherry, Ph.D., assistant professor in Wistar's Immunology Program and lead author of the study. Wherry conducted the research as a postdoctoral fellow in the Emory University laboratory of Rafi Ahmed, Ph.D., before joining Wistar earlier this year. "What we found was that the T cells in the chronically infected mice responded poorly to the vaccine."

Specifically, Wherry says, the T cells failed to proliferate, or expand in number. This failure to proliferate seemed to correlate with a high viral load, which suggests several directions researchers might pursue in improving response to therapeutic vaccines.

"The ongoing stimulus to the immune system that occurs in chronic infection seems to pre
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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
1-Jul-2005


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