GAITHERSBURG - Even as the number of new cases of severe acute respiratory syndrome seems to be slowing overseas, a team of scientists here is revving up its effort to keep people from getting infected in the first place.
Researchers at GenVec, a small biopharmaceutical company that normally fights enemies such as cancer and HIV, has begun the painstaking work it will take to come up with a SARS vaccine - if, that is, they can come up with one at all.
Their approach is among the newest in the field of vaccine research. Scientists plan to insert synthetic genetic bits of the coronavirus that causes SARS into a benign form of another virus, in hopes that the body will react to the hybrid in a way that will protect it from the illness.
"When it works, it's the best medicine you can do, because it prevents the disease," said Paul H. Fischer, GenVec's chief executive officer.
Bringing vaccines to market normally takes years; developing them involves trial and error, with no guarantee of success. Twenty years after the discovery of the AIDS virus, researchers have not found an effective vaccine against it.
The quest to develop a vaccine against SARS - which spreads quickly and has a relatively high mortality rate - has taken on great urgency among public health officials throughout the world. GenVec's effort, supported by a $420,000 grant from the National Institutes of Health, is one of many underway in public and private labs.
The point of a vaccine is to teach the body how to attack an invader before it invades, so it will be ready to launch a fight when the real thing comes along. Vaccines try to mobilize the two key weapons of the body's defense system: antibodies, proteins which kill or disable infectious organisms, and T-cells, which attack infected cells.
"It's kind of like tricking the body, in a way," said Fischer.
In many cases, the trick has worked. Along with clean water, vaccines have been one of the most successful public-health interventions, preventing millions of deaths from such scourges as tuberculosis, polio and smallpox.
To combat SARS, a new disease for which most people have no natural defense, GenVec is attempting to create a so-called DNA vaccine. Call it vaccine-making with a high-tech twist.
First, scientists take bits of DNA from an adenovirus, which is responsible for the common cold, weakening it so it can't replicate. Next, they insert snippets of SARS genes - in this case, blueprints for a protein found on the surface of the SARS virus - into the cold virus.
The hybrid can't replicate on its own because it's genetically crippled. So the scientists put it into other living cells to grow enough to use in a potential vaccine, said Jason G.D. Gall, the point man on GenVec's SARS effort.
It's not until six or eight weeks later that Gall and other members of his team can see the virus in a test tube with the naked eye. If all goes well, it looks like a fuzzy white band.
"A lot of hard work has paid off by then," said Gall, a 34-year-old microbiologist from California. "You've created a potential vaccine, and then you send it out to see if it can do what it was born to do."
GenVec scientists may have to repeat the process more than 10 times with different genetic ingredients, hoping to come up with one vaccine candidate.
Dr. Gary J. Nabel, director of the Vaccine Research Center at NIH's National Institute for Allergy and Infectious Diseases, which is expected to send the first two synthetic genes to GenVec this week, described the adenovirus as a "dumb carrier" for the genes.
"The important thing here is we've learned how to grow them in the laboratory and cripple them so they will not cause a cold when you use them in these vaccines," he said.
If the experimental vaccine works, the body will read the SARS genes, produce corresponding SARS proteins, then recognize them as foreign and launch an immune response.
Scientists at NIH and GenVec hope the response will be the most comprehensive kind: with both T-cells and antibodies. "Adenovirus does seem to induce a combination of both cell-mediated [T-cell] immunity and antibody immunity," said Nabel.
Nabel said the approach has yielded promising results in the effort to develop an Ebola vaccine, providing protection in nonhuman primates.
There are several ways of making vaccines because no single method always works. To make "inactivated" or "killed" vaccines, scientists grow large quantities of a germ, kill it using a chemical such as formaldehyde, then inoculate people with it. Dr. Jonas Salk used this method to make his poliomyelitis vaccine in 1955.
"It's a tried-and-true technique, at least for other viruses," said Nabel. "The downside is that any time we inactivate the virus, we're essentially distorting its structure."
Another concern is making sure that all of the virus is dead. One batch of the Salk vaccine mistakenly contained live virus and ended up infecting some people with polio.
So-called "live" or "attenuated" vaccines contain live germs, weakened to the point where they shouldn't cause serious disease. "When you can do it, it can be very powerful," said Nabel. Vaccines for measles, mumps and rubella rely on this approach
But scientists must know a lot about the behavior of the germ to use this technique, he said. The danger is that the living germ, even weakened, can mutate back to its virulent form and end up causing disease.
Another technique, used to make the hepatitis B vaccine, involves synthesizing proteins found in a germ and introducing them directly into the body. These are "sub-unit" vaccines.
Once GenVec has some potential vaccine candidates, the company will ship them back to the NIH for testing in animals. If one works, it could be used in clinical settings next year, at least experimentally.
No one knows how much of a threat that SARS will be by then, or if it will have fizzled out on its own.
"All of this work is insurance," said Fischer. "We all hope this thing's gonna go away."