Though offensive biological weapons research ended in the United States in 1969, researchers in biological defense did not end their quest for a vaccine to combat it because of its virulence.

Today, a new VEE vaccine is on the road to licensure because of fruitful research performed at the U.S. Army Medical Research Institute of Infectious Diseases.

The team that developed the vaccine was awarded a 2003 Army Research and Development Achievement Award that was presented Dec. 2 in Orlando, Fla.

"We're thrilled," said Dr. Doug Reed, the rookie on the team who's worked with VEE at USAMRIID since 2000. "We've had extensive collaboration and a lot of teamwork, so to see it rewarded is very exciting."

With a mild case of VEE, a victim will have a fever, muscle aches, and a headache that's so painful it's almost unbearable to move the head, said Dr. Mary Kate Hart, a member of USAMRIID's VEE vaccine team. Because the virus has a one-to-one infection case ratio, everyone who is exposed will get sick if they aren't vaccinated.

"For Soldiers on the battlefield exposed to an aerosol (of VEE virus), the effect would be devastating," she said. "Everyone who gets it is going to be feeling its effects at the same time, within 24 to 48 hours of exposure. And while the disease is not fatal to people in the military age group, it does place a huge demand on the medical system."

The current, unlicensed vaccine that most people who work with the VEE virus receive has its shortcomings. Called TC-83, the vaccine can mutate because it is a mixture of viruses, said Dr. Michael Parker of the VEE vaccine team.

"It was made by an old classical technology that was successful in making vaccines for polio and yellow fever," he said. "In some instances it caused disease for some of the vaccine recipients, and some people just didn't develop an immune response, so they needed an additional shot of the C-84," which supplements the TC-83 vaccine to produce an immune response.

The new vaccine, called V3526, is a live, attenuated vaccine like its predecessor, but it was derived by genetic engineering. In creating the vaccine, USAMRIID earned about half a dozen patents, including one for the vaccine as well as for techniques and technologies involved in making it.

"We've been able to go in and specifically design mutations that knock out the ability of the virus to cause disease," Parker said. "With the old technology ... these vaccine strains were derived randomly, by chance, in cell culture. What the new technology allows us to do is to go in and specifically decide what we're going to do, so it's kind of like taking a designer virus approach."

The team removed four amino acids in the virus that are critical to the ability of the virus to multiply, said USAMRIID's Dr. William Pratt.

"With this mutation the virus replicates so poorly that it does not cause disease but still replicates to sufficient levels to provide immunity," he said. "In addition, it can't revert to becoming a disease-causing virus, like the older one, and because it's a defined mutation, it can be easily tracked because there's only one version of the virus-- unlike the other vaccine that had multiple versions."

Initially the Army charged the group with coming up with vaccines for three types of VEE: 1E, 3A and 1AB. In the end, the V3526 met the requirements for all three.

"Instead of having a trivalent vaccine, we have a monovalent vaccine that provides protection," Hart said.

The team transitioned the VEE vaccine to the Joint Vaccine Acquisition Program in 1999 and continues to monitor it. They meet with Kathy Berst, the vaccine manager for VEE at JVAP, and stay apprised of its progress now that it is in the hands of DCV LLC, the prime systems contractor that is responsible for developing the vaccine and licensing it.

"USAMRIID developed the V3526 construct, so having them work on the team with the DVC vaccine development experts is really helpful," Berst said. "We rely on them as consultants."

This relationship with JVAP and DVC could offer long-term benefits for future vaccine work for eastern and western equine encephalitis.

"They know what we're striving for, so when they develop EEE and WEE vaccines, they're using the information that they have learned from the VEE transition," Berst said.

The entire process, Pratt said, has been a model of a successful program all the way from the basic research up to the clinical use.

"When a product transitions, it enters what the acquisition folks call the Valley of Death, because the tech base and the developers don't normally talk to each other before the handoff," he said. "We worked very hard to close this valley and try and make it seamless."

If all goes well with the FDA licensing and funding, VEE vaccine will be available for troops by 2013.

"The transition of VEE to JVAP and DVC was so successful because everyone involved wants to see this ultimately become a licensed product," said DVC President Terry Irgens. "We are very pleased with the quality of the vaccine candidate provided by USAMRIID's VEE team. We congratulate the team on their success and look forward to further collaboration."