Chimpanzee adenoviruses could be used to make vaccines, two new studies in the 4 January issue of the journal Science Translational Medicine report. The results hint that vaccines developed with chimp vectors can trigger immune protection against hepatitis C, a virus that affects the liver and is estimated to infect 170 million people globally. There are no vaccines to protect against the infection.
Human adenoviruses are commonly used as vectors—the DNA molecules used to carry genes into human cells—for delivering vaccines or for gene therapy. In vaccines, genes encoding antigens for a specific pathogen are packaged into the virus vector.
Once released into cells, the antigens kick immune cells into gear. But recent work indicates that human adenoviruses may not be the best vaccine vectors, because many populations have been exposed previously to these viruses. This preexisting immunity gets rid of the virus before it can stimulate a new immune response.
Figuring that most people are far less likely to pick up germs from chimpanzees, researchers are turning to chimpanzee adenoviruses as potential vaccine vectors. In one experiment, Stefano Colloca at the Italian biotechnology company Okairos and colleagues identified several new chimp adenoviruses and devised a screening strategy using mice to rank their immunological potency, a measure of their effectiveness as a vaccine vector. The team demonstrated that chimp adenoviruses are more potent and work better than most human adenoviruses.
An estimated 160 million people worldwide carry persistent hepatitis C virus infections (shown here as percent of the total population: Gray, no data; tan, >1.0 to 2.5%; light brown, 2.5 to 10%; dark brown, >10%). View a larger version of this image. | Image: B. Strauch/Science © 2012 AAAS
In a separate phase 1 clinical trial, Eleanor Barnes at Oxford University and colleagues used one of the chimp vectors from the Colloca study to deliver a potential hepatitis C vaccine to small groups of healthy human volunteers.
The chimp virus vector triggered a specific immune response to the virus (as did a rare human adenovirus vector), and appeared to be safe and well-tolerated.
Taking a closer look, the team saw that hepatitis C antigens from the vaccine activated memory T cells in participants. Once exposed to a particular pathogen, T cells help the body recognize and fight off future invaders. In a related Focus article in the issue, Michael Houghton of the University of Alberta discusses the findings and their implications for preventing chronic hepatitis C infection (vaccines cannot help people who are already infected).
“I think the results are very encouraging, not just for hepatitis C vaccine development, but more generally as well, said Paul Klenerman, a co-author on both studies and professor at Oxford University. “Producing such large populations of functional T cells could be of value in a variety of infections and potentially also cancers.”
5 January 2012