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Researchers Pursuing Nasal Anthrax Vaccine
Date:4/10/2008

Mice given combination version of immunization survived exposure, study reports,,,,

THURSDAY, April 10 (HealthDay News) -- American researchers have developed a nasal spray anthrax vaccine that provides protection against the potentially deadly bacterium, at least in mice.

By "detoxifying" and combining two of anthrax's lethal toxins, the researchers were able to develop a vaccine that appears to be more effective than vaccines that contain just one altered version of an anthrax toxin.

"This study is an early stage study," said one of the authors, Mingtao Zeng, an assistant professor in the department of microbiology and immunology at the University of Rochester Medical Center in New York. "It can be administered through the mucosa, and it generated an immune response and protected against anthrax. We're very excited about this."

Results of the study were published in the April issue of Clinical and Vaccine Immunology.

Anthrax is the infection caused by the naturally occurring bacterium Bacillus anthracis. These spore-forming bacteria are found in wild and domestic animals, such as camels, goats, sheep, cattle and deer. Spores can live in the soil for years. Naturally occurring anthrax infections are rare in the United States, according to the U.S. Centers for Disease Control and Prevention.

Anthrax can also be used as a bioterrorism weapon, as evidenced in 2001, when terrorists mailed letters containing anthrax spores to 22 U.S. men and women, five of whom died. Iraq's Saddam Hussein developed anthrax spore-filled weapons, and Boris Yeltsin said the former Soviet Union had an anthrax weapons program far larger than pre-war Iraq's, according to background information with the study.

Anthrax can be effectively treated with antibiotics, if the infection is caught in its early stages.

There is a U.S. Food and Drug Administration-approved anthrax vaccination that is reported to be 93 percent effective, according to the CDC. After the 2001 anthrax attacks, the federal government required vaccination for military personnel deployed in high-risk areas. The FDA-approved vaccine is given as an injection and must be administered in three doses, scheduled two weeks apart. Then, to remain effective, booster shots must be given at six, 12 and 18 months, and then again each year after for maximum protection, according to the CDC.

"Unfortunately, to make this vaccine work, you have to administer boosters," explained Philip Tierno, director of clinical microbiology at New York University Medical Center, and author of Protect Yourself Against Bioterrorism. And, the need for boosters isn't always practical in military situations, he said.

Anthrax can be deadly, because it secretes three toxic proteins: protective antigen (PA), lethal factor (LF) and edema factor (EF). Interrupting the action of any of these proteins can provide protection against anthrax. Tierno said the FDA-approved vaccine relies on disrupting PA's action.

In an attempt to simplify the vaccine procedure, so it could be administered nasally and without the need for so many booster shots, the University of Rochester researchers "detoxified" the lethal factor, creating what they called mutant lethal factor (mLF). Then they combined mLF with PA and tested each component and the two together on mice.

When exposed to 100 times the lethal dose of anthrax, 60 percent of the mice immunized with PA survived, and 30 percent of those given mLF alone survived. Yet, the mice given the combination vaccine were completely protected.

"There seems to be a synergy with the use of PA and mLF that is even better than either alone," Tierno said.

Zeng said the next step for the Rochester researchers is to test the experimental vaccine in other animals to be sure it's safe and effective. Then, they hope to get the vaccine from a three-dose regimen down to a one-time vaccination.

And, the current version of the experimental vaccine needs to be refrigerated, but Zeng said he suspects that it could be changed to a powder form for easier portability. But, right now, he added, the researchers are focusing on making the vaccine as effective as they can.

More information

To learn more about anthrax infections, visit the U.S. Centers for Disease Control and Prevention.



SOURCES: Mingtao Zeng, Ph.D., assistant professor, department of microbiology and immunology, University of Rochester Medical Center, Rochester, N.Y.; Philip Tierno, Ph.D., director, clinical microbiology, New York University Medical Center, New York City; April 2008, Clinical and Vaccine Immunology


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