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Racing to find a vaccine

By Alison Walker, News-Post Staff

FREDERICK -- Despite existing antibiotics and vaccines to treat and prevent anthrax, scientists aren't resting on their laurels four years after mail attacks in 2001 that killed five people.

"We have to be looking ahead, thinking about what problems there might be in the future," said Arthur Friedlander, a senior scientist and anthrax expert at the U.S. Army Medical Research Institute of Infectious Diseases, the Army's biodefense laboratory at Fort Detrick.

"We think we have approaches to dealing with this organism now, but we can't be complacent about it," Mr. Friedlander said. "This (anthrax) was the one organism that was used."

Though an effective anthrax vaccine is available and a new one is in clinical testing, USAMRIID is one of several laboratories around the country studying additional ways to protect the body against anthrax.

New treatments would be critical in fighting infections caused by genetically engineered anthrax bacteria, Mr. Friedlander said. Anthrax strains with manufactured resistance to current vaccines and antibiotics remain a threat.

Next-generation anthrax

Several biopharmaceutical companies are developing next-generation vaccines against anthrax, an improvement on the licensed vaccine, anthrax vaccine adsorbed.

The next-generation vaccine, developed by Mr. Friedlander and a USAMRIID team, uses protective antigen, a protein secreted by the anthrax bacterium.

The protein, dubbed rPA, induces the body's immune system to produce antibodies against the bacteria's toxin and has been shown in USAMRIID studies to give a high level of protection against inhalation anthrax in nonhuman primates.

The National Institute of Allergy and Infectious Diseases, under the National Institutes of Health, is conducting clinical trials on the rPA vaccine.

The U.S. Department of Health and Human Services awarded VaxGen an $877.5 million contract in November 2004 to fund 75 million doses of rPA anthrax vaccine for the national stockpile, which could immunize 25 million people after a large-scale anthrax attack.

Protective antigen is the most protective protein ever discovered and the rPA vaccine is extremely effective, Mr. Friedlander said.

Mr. Friedlander's team announced May 1 a combination of anthrax adsorbed vaccine and antibiotics significantly improves survival after exposure. The study also suggested the combination treatment may allow for a shorter course of antibiotics. Antibiotics are typically prescribed for 60 days after exposures.

In their study, all monkeys exposed to airborne anthrax spores and treated several hours later with the vaccine and antibiotics survived and never developed infection. Only 44 percent of monkeys given just antibiotics survived.

Mr. Friedlander said he expects a similar study combining antibiotics and rPA vaccine, rather than anthrax adsorbed, would show equally good protection post-exposure against inhalation anthrax.

Boosting protection

Despite the vaccine's proven effectiveness in animal models, USAMRIID is studying additional components that could boost rPA's protection against anthrax.

"(rPA is) a spectacular vaccine," he said. "It's not as if it's not a superior vaccine -- that's why it was selected for advanced development."

One area of study by USAMRIID and other laboratories is a vaccine using both rPA and a capsule that surrounds the anthrax bacterium. The capsule makes the bacterium slippery, preventing the body's white blood cells from destroying it.

A vaccine based on this capsule allows the body to make antibodies that bind to the capsule, enabling white blood cells to destroy the bacteria.

USAMRIID proved the capsule vaccine provided protection against anthrax in mice in a late 2004 study. Mr. Friedlander said researchers are planning additional animal studies, including tests in nonhuman primates.

A combination of both rPA vaccine and capsule vaccine could provide considerable protection, he said, as each targets a different mechanism the bacteria uses to infect a host.

Targeting anthrax genes

USAMRIID researchers are also knocking out genes in the bacterium to determine the role each plays.

New therapies will target these abilities. Penicillin, for example, interferes with the bacteria's ability to make cell walls and divide.

Developing improved antibiotics involves studying what the anthrax bacteria need to survive in a host and to subvert the body's immune response, Mr. Friedlander said.

"If you damage one pathway, it doesn't necessarily mean the organism's going to stop growing," he said. "There's a lot of redundancy built in -- they're not stupid. Finding a critical, vital target remains a challenge."

Research will need to stay one step ahead of the anthrax bacteria to ward off the threat of antibiotic-resistant organisms, Mr. Friedlander said.

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