Experimental Vaccine Stops SARS in Its Tracks

Animal study shows promise, but human application uncertain

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HealthDay Reporter

WEDNESDAY, March 31, 2004 (HealthDayNews) -- An experimental DNA vaccine against SARS has succeeded in preventing the coronavirus from replicating in laboratory mice.

"This study is important for two reasons," says senior study author Dr. Gary J. Nabel, director of the Vaccine Research Center at the National Institute for Allergy and Infectious Diseases (NIAID). "It is the first depiction of immune protection by vaccine for the SARS, and, because we have such good understanding of the mouse immune system and mouse genetics in general, we were able to make good progress in defining mechanisms of protection."

But this early success is no guarantee the idea will translate into an effective vaccine for humans.

Given the scope of the SARS outbreak last year, a vaccine could become a much needed weapon if the virus resurfaces. According to the latest figures from the World Health Organization, 8,437 people were infected and 813 people died between Nov. 1, 2002, and July 31, 2003. China, Asia and Canada were hardest hit. This year, experts aren't sure what the future will hold.

The concept of a DNA vaccine has been around for a long time and has even had some success stimulating immunity against influenza, HIV, Ebola, West Nile and other viruses in animal models. But a similarly successful vaccine that works in humans has so far been elusive.

"I've been a little skeptical about DNA vaccines over the years because they haven't panned out yet, plus they're sort of a whole new concept," says Robert Garry, an immunology specialist at Tulane School of Medicine in New Orleans.

But, he adds, "this sounds about as promising as anything I've heard from a DNA vaccine."

Most vaccines currently used in humans employ killed or weakened forms of a whole virus or bacteria. These altered organisms are injected into a person to stimulate the immune systems to produce antibodies against the infection.

The idea behind a DNA vaccine is to inject a modified version of the DNA of an infectious virus or bacteria into a person. Once inside the person, the DNA will cause proteins to be made that will then stimulate the person's immune system.

"It's an attractive idea from the point of view of being able to manipulate the cloning and sequencing of proteins," Garry says. "It's a one-step process: just clone the gene, then inject the cloned DNA into the recipient."

The authors of this study, who report their findings in the April 1 issue of Nature, constructed their vaccine from a segment of DNA that codes for a protein found on the outer surface of the SARS virus. The purpose of the protein in normal SARS viruses is to help the virus enter and infect living cells.

Once the DNA segment was injected into the mice, it instructed the cells to make a protein similar to that found on the surface of the SARS virus. These proteins then triggered the immune system to respond. There was not enough DNA to actually cause infection.

The researchers tested two versions of the vaccine with differing amounts of genetic material. Two groups of mice each received three doses of one of the vaccines over a period of six weeks. A control group of mice received blank vaccines.

Thirty days later, all the mice were exposed to the live SARS virus. Two days after that, the mice in the control group showed high levels of the virus in their lungs. Both groups of vaccinated mice had almost nonexistent levels of the virus -- one million times fewer virus particles than the unvaccinated mice.

There are several issues in trying to extrapolate data from rodents to humans. For one thing, mice do not actually get sick from SARS, even though the virus does replicate in their respiratory tract.

"The mouse isn't a person," Garry explains. "It's a smaller animal, it metabolizes faster, it doesn't live as long, and it doesn't get sick, so it's probably easier to protect against SARS."

This is, however, "at the moment no better model available," Nabel says.

Nabel sees research progressing on a "dual-track process" with ongoing animal studies happening at the same time as exploratory human studies.

In fact, NIAID announced that Vical Inc. of San Diego is manufacturing a highly purified vaccine suitable for human clinical trials, pending approval from the U.S. Food and Drug Administration. Phase I trials may start by the end of this year, Nabel says.

But ultimate FDA approval is unlikely to come overnight. "I have a little bit of concern that regulatory agencies, once somebody finally brings something like this to the market, are going to have a whole lot of hoops to jump through," Garry says. "If these things had come out like gangbusters, I think that would be one thing. Since they haven't really proven to be a panacea, I think the regulatory agencies like the FDA are going to look at them a lot more skeptically."

More information

Visit the National Institute of Allergy and Infectious Diseases or the U.S. Centers for Disease Control and Prevention for more on SARS.

SOURCES: Gary J. Nabel, M.D., Ph.D., director, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Robert Garry, Ph.D., professor, microbiology and immunology, Tulane School of Medicine, New Orleans; April 1, 2004, Nature

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