University Receives NIH Grant to Study New Rabies Vaccine that Clears Virus From Brain

D. Craig Hooper, PhD, of the Director of the Center for Neurovirology at Thomas Jefferson University, (right) and Bernhard Dietzschold, DVM, a professor of microbiology and immunology.

Thomas Jefferson University announces it has received a $4.8 million grant from the National Institutes of Health (NIH) to test a new rabies vaccine with the potential to cure the virus infection, even after it has made its way into a persons central nervous system (CNS). Today, if an unvaccinated person is infected with rabies and it spreads to the brain, there is little chance for survival.

The grant to study the new vaccine, which was developed by Jefferson researchers, including the principal investigator for the project, D. Craig Hooper, PhD, director of the Center for Neurovirology, will be shared among Jefferson, the University of Georgia, the Medical College of Wisconsin and the Institute for Hepatitis and Virus Research (Pennsylvania Commonwealth Institute).

The rabies vaccine used today to protect people from the virus is the same one used to treat a person who has been bitten by a rabid dog, raccoon, bat or other animal. If the vaccine series and preformed rabies virus neutralizing antibodies are administered shortly after the bite, the virus is destroyed and the person almost always survives. For someone who unknowingly contracts rabies or is not treated, flu-like symptoms generally begin to manifest within a few weeks, meaning the virus has reached the nervous system and survival is unlikely. About 50,000 people die worldwide every year after being infected with the virus, most of whom live in developing nations where dog rabies is not controlled and vaccines for humans can be hard to get and expensive. A new version of the rabies vaccine that is effective after someone develops the first signs of the disease could be the saving grace for some of these people. Recently, several patients whose brains were infected with the virus survived, confirming studies in animal models that under certain circumstances the immune system can clear rabies virus from the brain.

Hooper, along with Jefferson colleagues, Bernhard Dietzschold, DVM, a professor of microbiology and immunology and Milosz Faber, PhD, a research instructor in microbiology and immunology, hypothesized that a weaker strain of the virus can be used to cause the immune system to eliminate more deadly virus strains. Studying the mechanisms by which the immune system can wipe the virus from the CNS and the development of weakened virus strains with improved safety profiles that can induce this process have been the focus of their research, and is the basis for the vaccine being tested in the NIH-funded study.

"This is the first translational work to be done on live-attenuated rabies vaccines with the potential to clear wild-type rabies virus from the central nervous system," says Hooper, who is also an associate professor of cancer biology with a joint appointment in neurological surgery at Jefferson. "This live attenuated vaccine can clear a pre-existing infection with a highly lethal virus from the brains of mice, an outcome that we have never seen before.

"This grant lets us further study the potential that this vaccine has for humans, will give us information on biomarkers of rabies virus infection and the protective immune response, and will help us predict the maximum post-infection delay where treatment may be possible." Also, if it is found safe and effective, the vaccine will serve as a foundation to develop similar reagents for the treatment of epidemic virus infections of the brain, a major health concern, particularly with respect to bioterrorism. "The ultimate goal is to develop a single vaccine that can safely clear several types of encephalitis viruses from the CNS tissues," he says.

The principal investigators at the other institutions include Zhen Fu, DVM, PhD, University of Georgia; Rodney Willoughby, MD, Medical College of Wisconsin; and Songming Chen, PhD, Institute for Hepatitis and Virus Research.