Jefferson scientists show rabies has potential use in vaccines for other infectious diseases

06/11/04

Rabies may hold a key to developing a vaccine against anthrax

Scientists at Jefferson Medical College have literally "fused" a part of a rabies virus protein to another foreign protein, resulting in a more robust immune response in animals than with the protein alone. Though it's early in the research, the researchers, in demonstrating that it's possible to make a foreign protein more "immunogenic," have opened the door to creating more powerful vaccines against a number of infectious agents, such as anthrax.

Matthias J. Schnell, Ph.D., associate professor and acting chair of biochemistry and molecular pharmacology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and his colleagues including internationally renowned virologist Hilary Koprowski, M.D., professor of microbiology and immunology at Jefferson Medical College and director of the Biotechnology Foundation Laboratories and the Center for Neurovirology at Jefferson Medical College, and Bernhard Dietzschold, D.V.M., professor of microbiology and immunology at Jefferson Medical College report their results June 14, 2004 in the online version of the Proceedings of the National Academy of Sciences. The article is scheduled to appear June 22 in the print edition of the journal.

According to Dr. Schnell, who is also associate director of the Center for Human Virology and Biodefense at Jefferson Medical College, a protein inside the rabies virus called a nucleoprotein is wrapped around the virus genetic material, forming a "viral ribonucleoprotein complex" (RNP). The researchers knew that the nucleoprotein was able to arouse a strong immune response, causing an infected host to send out waves of antibodies and other immune system cells. They wanted to see if they could use this effect to enhance the response to a foreign protein.

They created a new rabies virus that included the gene for green fluorescent protein (GFP), a harmless protein that glows green, in the rabies virus structure. The new virus produced a "fusion protein" consisting of rabies nucleoprotein and green fluorescent protein. This was incorporated into the rabies RNP and into virus particles.

The Jefferson team found that mice injected with the new viral RNP had a stronger, longer-lasting immune response, producing greater amounts of viral antibodies.

"First, we were able to show that when we fused a foreign protein green fluorescent protein to the rabies virus nucleoprotein, the resulting fusion protein was incorporated in ribonucleoprotein (RNP) capsids," Dr. Schnell says.

"But what is so exciting is that if we immunize mice only with GFP, we don't see any seroconversion," he explains. "The fusion protein seroconverted the mice against GFP. Clearly, the nucleoprotein helps to enhance the immune response against the other protein. This is proof of principle a first step." The results indicate that scientists can now use the rabies virus as a vehicle through which vaccines can be made against other infectious agents, says Dr. Schnell.

He suggests that the technique will prove invaluable, for example, in creating a longer-lasting vaccine against anthrax than currently is available.

"Rabies virus is appropriate to use because killed rabies virus is used as a human vaccine already," he notes. "We believe that if we use GFP, which is poorly immunogenic, and we couple it to rabies nucleoprotein and get a nice immune response, the next logical step is to put something such as the 'protective antigen' of anthrax to it."

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