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Fighting fire with fire? Vaccine based on chimp virus shows promise against HIV

strengths of a human adenovirus vaccine without the drawback of pre-existing immunity in its target population.

Because HIV infects only humans and chimpanzees, the current study used a sophisticated mouse model to test the new vaccine. For this model, the researchers first incorporated an internal HIV protein known as gag into the modified chimpanzee adenovirus vaccine. They also engineered a matching vaccine that incorporated gag into the human adenovirus. They then used a variant of the vaccinia virus, which can infect mice, that included the gag protein. For comparison, some mice were exposed to the human adenovirus, so that they would demonstrate the pre-existing immunity to the virus seen in many humans.

After vaccination with the chimpanzee adenovirus vaccine, the mice mounted a powerful T-cell-based immune response and were able to fight off experimental infection by the vaccinia virus containing gag, the HIV protein. The mice pre-exposed to the human adenovirus and vaccinated with the human adenovirus vaccine, however, demonstrated significantly weaker immune responses to the vaccinia virus.

"It's hard to say that because the vaccine works well in a mouse model, it will protect humans from HIV infection," Ertl cautions. "But we do know that the kind of immune response we saw in mice can protect non-human primates infected with SIV from developing disease." SIV, or simian immunodeficiency virus, is the chimpanzee counterpart to HIV, or human immunodeficiency virus.

In addition to moving forward with testing of the chimpanzee adenovirus vaccine against HIV, Ertl and her colleagues are developing similar vaccines against rabies, smallpox, and a number of other viruses.

Julie C. Fitzgerald, a graduate student in senior author Ertl's laboratory, is lead author on the Journal of Immunology study. The other Wistar-based authors are Zhi Q. Xiang, Anthony P. Wlazlo, and Wynetta Giles-Davis. Arturo Reyes-Sandoval is affiliated
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Contact: Franklin Hoke
hoke@wistar.upenn.edu
215-898-3716
The Wistar Institute
3-Feb-2003


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