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Chimpanzee virus may be key to better vaccines, study shows

PHILADELPHIA - Immunologists know that human adenoviruses, a common cause of respiratory-tract infections in people, can be retooled in the laboratory to serve as effective vaccines against an array of viral diseases. When genetically engineered to express selected genes from other viruses - such as rabies, HIV, smallpox - adenoviruses infect human cells without doing them lasting damage and stimulate a vigorous, long-lasting immune response when they do so.

That's the theory, anyway. But there are significant problems with the theory. Adenoviruses are nearly ubiquitous among humans, so much so that a third or more of the population have neutralizing antibodies circulating in the blood able to inactivate an adenoviral-based vaccine.

Now, in a new proof-of-principle study in mice, researchers at The Wistar Institute and the University of Pennsylvania have shown that a vaccine based on a chimpanzee adenovirus possesses the immunological strengths of a human adenovirus vaccine without its drawbacks. The study appears in the March issue of the Journal of Virology.

"The chimpanzee adenovirus vaccine works like a charm," says Hildegund C.J. Ertl, M.D., a professor at The Wistar Institute and senior author on the study. "It's immunologically potent, and it's clear from our study that it would not be inactivated due to viral pre-exposure, as vaccines based on human adenoviruses can be."

For the study, the scientists developed two prototype vaccines against the rabies virus. One was a human adenovirus that incorporated one rabies gene, and the other was a chimpanzee adenovirus with the same gene. In mice unexposed to either type of adenovirus, the vaccines both elicited strong antibody responses. In mice pre-exposed to the human adenovirus, however, the vaccine based on the human adenovirus was severely compromised, while the one based on the chimpanzee adenovirus maintained its effectiveness.

Ertl and her coworkers are now working
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Contact: Franklin Hoke
hoke@wistar.upenn.edu
215-898-3716
The Wistar Institute
6-Mar-2002


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