News Release

Jefferson virologists create rabies virus-based vaccine against HIV

Peer-Reviewed Publication

Thomas Jefferson University

Researchers at Jefferson Medical College are using a new ploy to combat HIV, the AIDS virus: Rabies.

Scientists have devised for the first time an HIV vaccine using a weakened rabies virus to carry a piece of the HIV "coat" into a cell. In rousing the body into making anti-HIV antibodies, they may have found a way to effectively turn on the immune system against the virus. The work, which for now is limited to tests in mice, lends hope to eventually designing such a vaccine against HIV in humans.

The researchers, led by Matthias Schnell, Ph.D., assistant professor of biochemistry and molecular pharmacology, and Roger J. Pomerantz, M.D., professor of medicine, biochemistry and molecular pharmacology, chief of the division of infectious diseases, and director of the Center for Human Virology, both of Jefferson Medical College of Thomas Jefferson University in Philadelphia, report their findings March 28 in the Proceedings of the National Academy of Sciences.

Using the rabies virus as a vehicle for a vaccine is novel, says Dr. Pomerantz. "The rabies virus is the vehicle to get an HIV envelope protein to express itself, thus getting the attention of the immune system," he says. "It's not only the first use of a rabies virus for an HIV vaccine, it's the first use of a whole group of viral vectors -- non-segmented negative-stranded RNA viruses -- for HIV vaccines."

The scientists took a weakened, safe, live rabies virus and inserted the HIV-1 gp160 envelope protein gene, creating a "recombinant" rabies virus. They then injected the rabies-HIV package into mice. The gp160 gene actually manufactured the gp160 protein, which is normally part of the HIV outer jacket. The scientists found that the mouse immune system was able to recognize this protein and began to develop antibodies against HIV, as well as releasing white blood cells called cytotoxic lymphocytes, which kill virus-infected cells. The scientists had to give the mice a booster -- an additional injection of a different HIV protein, gp120 -- to kick-start the immune system to release anti-HIV antibodies.

Drs. Schnell and Pomerantz's teams looked at three groups of five mice: one group was infected with rabies virus not expressing HIV as a control; and two groups expressing different varieties of HIV. Nearly all of the mice in the latter two groups responded to the HIV attack, sending out lymphocytes and antibodies.

The researchers are now also working on using the same approach against other viruses such as hepatitis C.

"Our goal was to devise a live viral vaccine for HIV," Drs. Schnell and Pomerantz explain. But previous attempts at creating a killed virus vaccine have proven ineffective. "We've learned that a killed virus vaccine is not immunogenic enough. The theory is to create a live virus vaccine that continues to express HIV antigens and the immune system will continue to see it and it will be like an attenuated HIV virus but you won't have to actually use HIV. That's the key -- no one has been able to agree that using an attenuated HIV is safe. This allows HIV proteins to keep being presented in a harmless way." The scientists would like to continue testing the vaccine in more mice and then in other animal models in collaboration with scientists at the University of California at Davis. Those studies will likely begin in the next few months.

"Vaccines that are licensed now are either killed or attenuated," Dr. Pomerantz explains. "Using a viral vector for a vaccine has never been approved in humans. This would be a new approach to a vaccine -- you're using another virus as a vector to immunize against a second virus."

Much research remains to be done. "This is only in mice so far," Dr. Pomerantz says. "We still have to prove it's safe, and it will work against other worldwide HIV strains and in other animals. There's never been an approach that fully works in non-human primates, for example. That's the Holy Grail.

"There's been a lot on HIV vaccines in the last 15 years," Dr. Schnell says. "It's very promising, but we by no means yet have the definitive HIV vaccine."

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