Use of Chimpanzee Adenovirus Improves Vaccine

Researchers at The Wistar Institute (Philadelphia, PA, USA) and the University of Pennsylvania (Philadelphia) report in the March 2002 issue of the Journal of Virology that a vaccine based on a chimpanzee adenovirus possesses the immunological strengths of human adenovirus vaccine without its drawbacks.

Human adenoviruses can be genetically engineered to express selected genes from other viruses such as rabies, HIV, and smallpox. Adenoviruses infect human cells without doing them lasting damage and stimulate a vigorous, long-lasting immune response when they do so. However, adenoviruses are nearly ubiquitous among humans, so much so that a third or more of the population has neutralizing antibodies circulating in the blood able to inactivate an adenoviral-based vaccine.

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

"The chimpanzee adenovirus vaccine works like a charm, says Hildegund C.J. Ertl, M.D., a professor at The Wistar Institute and senior author of 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.”

While the starting material for the vaccine is a chimpanzee adenovirus, there actually is no chimpanzee involved in the process. To prevent any type of contamination that could originate in chimpanzees, the vaccine is synthesized, molecule by molecule, from the genetic code for the viral carrier – the chimpanzee adenovirus, in this case - and for the gene or genes to be incorporated, such as the rabies gene in the current study. The genes that coordinate replication of the virus are deleted.

"Because of the laboratory methods used to generate this vaccine, there is no danger of giving people an unknown virus or other entity from the chimpanzee,” says Dr. Ertl. She and her coworkers are now working on similar prototype vaccines against HIV, smallpox, and other viruses.