As the threat of anthrax-based bioterrorism chills the American public, work continues on a new and improved anthrax vaccine in the laboratories of the Virginia-Maryland Regional College of Veterinary Medicine at Virginia Tech.

There, researchers and technicians in the Center for Molecular Medicine and Infectious Diseases (CMMID) are using recombinant DNA technology to develop improved vaccines and diagnostic procedures for several organisms, some of which are considered biological warfare agents.

Yet it is CMMID's anthrax work that has captured recent media and public attention, including worldwide coverage on the BBC's "NightNews" program. Anthrax-contaminated mail in national media and federal government offices has caused four deaths (as of late November) and changed the way the American people look at their mail.

Bacillus anthracis is a large, naturally occurring, spore-forming bacterium, and it enjoys a rather ignominious position in the history of microbiology. In 1877, microbiologist Robert Koch, known for the famous "Koch's Postulates," cultured the organism and demonstrated for the first time that a bacterium could cause disease.

"Anthrax can be a deadly organism, but people should remember that America remains an endemic country for anthrax," says Dr. Nammalwar Sriranganathan, a veterinarian and microbiologist who is working on the new vaccine in the CMMID. Naturally occurring cases of the zoonotic bacterial disorder are still found in some domestic livestock and in wildlife and there are occasional human exposures, Sriranganathan says.

But there are characteristics of the organism and the disease it causes that make it an ideal agent for bioterrorism, Sriranganathan says. Anthrax can be deadly, it can be produced in dangerous quantities using readily available supplies and equipment, and it can be spread in several ways, ranging from the mail system, as we have seen, to crop-dusting airplanes.

One of the reasons the anthrax organism is so well-suited for this craven application is because of its ability to evolve into a dormant state known as a "spore." This highly protective capsule can withstand light, heat, and other environmental threats and is extremely durable and long lasting. One form of bacillus spore unearthed in a Utah salt mine was determined by carbon dating to be about 300 million years old, Sriranganathan says.

Anthrax is infectious but not contagious. That means that a person suffering from anthrax cannot pass the disease to another.

Anthrax causes three forms of disease, according to Sriranganathan. The cutaneous, or skin, form causes less serious disease and is easily treated. Cutaneous anthrax can be contracted by a person through an open wound from an infected animal or a spore-contaminated piece of mail. The second form, systemic anthrax, attacks the gastrointestinal system and might occur after eating tissues or bone from a contaminated animal. Even this form is treatable when antibiotic therapy is initiated early enough.

It is the pulmonary, or inhalation, form of anthrax that poses the greatest risk to human health, Sriranganathan says. The four deaths caused by anthrax were caused by pulmonary anthrax, which can be effectively treated with antibiotics following exposure but may be difficult to detect before clinical signs develop. Once clinical signs--which may vary but can include headache, swelling, fever, aches, and other flu-like symptoms--develop, antibiotics are not as effective. Pulmonary anthrax causes the lungs to fill with fluid, and blood poisoning and massive internal hemorrhaging soon follow.

Scientists believe that bacterial load and a person's immuno-competence play a role in whether or not the disease is contracted after exposure. The scientific community remains unsure about the possibility of collateral contamination within the mail supply but know that the amount of anthrax spores one is exposed to is a critical factor in the onset of disease. Most believe that a bacterial insult of at least 10,000 spores is required in order to cause pulmonary anthrax.

The fact that anthrax has leaped from a once vague and distant fear to an everyday threat has increased the urgency of the researchers' work.

With more than $1 million in funding from the U.S. Army, Sriranganathan, Gerhardt Schurig, and Stephen Boyle are developing a new anthrax vaccine for people and animals. A 15-year effort that culminated with the development, approval, and marketing of the RB-51 brucellosis vaccine (which now serves as the global standard) in 1996 has provided the foundation for the current work, which is focused on the production of multi-valent vaccines that can confer immunity to several different diseases through the administration of a single innoculation.

Anthrax has two virulent properties, an anti-phagocytic glutamic acid capsule and a tripartite toxin. The tripartite toxin includes lethal factor, edema factor, and protective antigen (PA), the latter of which is required in order for the first two components to cause the disease. So far, the researchers have synthesized the portions of Bacillus anthracis DNA that code for PA, used recombinant DNA technologies to introduce those fragments into the RB-51 platform, and achieved successful production of PA. By precisely challenging the immune system to develop a response to the PA alone, the researchers hope to create a vaccine that confers greater immunity with fewer side effects. Work is presently focused on evaluating the efficacy of the levels of PA that are expressed by the new vaccine.

The researchers are beginning to test the vaccine with laboratory animals. Once those trials are satisfactorily completed, the next step would be to test the vaccine with primates, most likely in conjunction with the U. S. Army Medical Research and Development Command at Fort Dietrick in Frederick, Md.

Following the completion of that work, the vaccine would need to be approved by the Food and Drug Administration and the U.S. Department of Agriculture before it could be licensed for use.

While the work is still several years away from completion, Sriranganathan says that people should be comforted by the fact that the government and the military have been preparing to deal with this sort of problem for a long time.

Sriranganathan believes we will likely see more anthrax cases in animals in the future as a result of the recent bioterrorist incidents. Most likely, they would come as a result of collateral contamination as opposed to pure agri-bioterrorism because if a person or group wished to commit a bioterrorist act against American agriculture, they would most likely use a more contagious agent, such as foot-and-mouth disease, he says.

Sriranganathan adds that the entire public health and agricultural community has increased surveillance and is on high alert for suspicious clinical signs in people and animals, which will help officials contain and cope with any disease outbreaks that may occur in the future as a result of terrorist activity.