Backup strategy? Chimp adenovirus vaccines may have an edge over those that use the human version, shown here in an electron micrograph (hexagon shapes).

Aping a Well-Studied Vaccine Strategy

A chimpanzee virus could provide a useful alternative for vaccine development, according to new research in mice. The work skirts a problem that has cropped up in experimental vaccines made from a similar human adenovirus--they don't work if you've already been exposed to the natural virus. The chimpanzee virus could be used to make vaccines to various pathogens, including hepatitis, human papillomavirus, and HIV.

Adenoviruses are a common culprit of upper respiratory and stomach ailments, and the immune system attacks them vigorously--more vigorously, in fact, than commonly used vaccine viruses. Consequently, researchers seized on adenoviruses, altered to be harmless, as potentially useful vaccines. When a gene from a dangerous virus, such as rabies or measles, is spliced into the adenovirus genome, the immune system battles both the adenovirus and the inserted gene. The individual then becomes immune to the disease-causing virus.

Despite their popularity--several HIV vaccines are in development using human adenoviruses--the approach has a significant drawback. Because the viruses are so common, about a third of the population have developed immunity to them by adulthood. The immune system of these people destroys the vaccine instead of generating antibodies to the disease gene it carries.

The chimpanzee adenovirus is an alternative, says virologist Hildegund Ertl of the Wistar Institute in Philadelphia, Pennsylvania, and her colleagues. To test its efficacy as a vaccine, they spliced a rabies gene into a chimp adenovirus engineered to be unable to reproduce. Then they inoculated mice with this vaccine, and, for comparison, another made from human adenovirus. Both vaccines produced immunity to rabies in mice previously unexposed to either adenovirus. But in mice that had been exposed to human adenovirus, only the chimp virus-based vaccine worked, the researchers report in the March issue of the Journal of Virology. Now, the team is developing a similar vaccine targeted to HIV, which they plan to begin testing in primates within the next few months. By cloning the virus and producing it in the laboratory, Ertl and her colleagues say they circumvent the danger of transmitting other chimp viruses along with the adenovirus.

"It's a nice tool to have in our arsenal," says virologist Gary Nabel, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. "Should we run into problems with prior immunity, we'll have something in our hip pockets."

Related sites
Abstract of the paper, from the Journal of Virology
Ertl lab home page
Nabel lab home page
Adenovirus information from CDC
Adenovirus resources, from Virology.net