Promising Anthrax Vaccine May Act Quickly to Halt Disease, Weill Cornell Medical College Experts Report

Weill Medical College of Cornell University
Friday, 21 November 2003

Scientists at Weill Medical College of Cornell University have created a single-shot anthrax vaccine that could one day be used to rapidly protect people in the event of a bioterrorism attack. A new study, conducted in an animal model and published in this month's journal Human Gene Therapy, suggests that the experimental vaccine may act more quickly and effectively than a recombinant protein vaccine being developed by the U.S. military.

The new vaccine, developed by Dr. Ronald G. Crystal, Chairman of the Department of Genetic Medicine at Weill Cornell, consists of genetically engineered anthrax toxin linked to human adenovirus, a common respiratory virus. The adenovirus is crippled so that it is unable to cause an infection, but the virus-toxin combination spurs the immune system to recognize and attack the toxin produced by anthrax, a potentially deadly bacterium.

Dr. Crystal and his colleagues found that the adenovirus-based vaccine offered mice nearly three times the level of protection one month after immunization as the U.S. military vaccine. About 72 percent of mice exposed to anthrax a month after vaccination with the adenovirus vaccine survived compared with just 27 percent of those given the U.S. military vaccine.

Even when anthrax exposure occurred just 11 days after vaccination, the adenovirus-based vaccine offered some protection -- 27 percent of mice survived -- compared with none of the mice given the new U.S. military recombinant protein vaccine.

"This type of response would be highly desirable in the event of a bioterrorism attack with anthrax," said Dr. Crystal, who is also Chief of the Division of Pulmonary and Critical Care Medicine and Director of the Belfer Gene Therapy Core Facility at Weill Cornell. "It is most likely that vaccines against potential bioterrorism agents will be stockpiled rather than used prophylactically. In that scenario, you want to have a vaccine that works as rapidly as possible to help protect as many people as possible."

While anthrax can be treated with antibiotics if caught early enough, treatment is not always successful. Anywhere from 50 percent to 75 percent of those with the most dangerous form of anthrax infection, inhalation anthrax, may die, even with antibiotic treatment.

While vaccination would prevent the illness from ever occurring, anthrax vaccination has been problematic. A U.S. vaccine developed in the 1960's requires six injections and an annual booster to confer protection. In the past, concerns about the safety and efficacy of the vaccine led some U.S. soldiers to face disciplinary action rather than agree to routine vaccination. And production problems by the manufacturer led to shortages for the U.S. military.

After 22 cases of anthrax, including five deaths, during a series of postal mail attacks in 2001, the need for a safe and effective vaccine became even greater. Because anthrax spores can be weaponized relatively easily, most experts agree the germ is high on the list of potential bioterror weapons.

"The experience with the anthrax attacks of 2001," observed Dr. Crystal, "was a wake-up call for how vulnerable our society is to bioterrorism. These 'bugs' are not hard to get a hold of, and the technology required to produce sufficient amounts to cause social havoc is not very difficult. Biotechnology gives us the weapons to protect ourselves, and vaccines are important components in that armamentarium."

Dr. Crystal said the adenovirus-based vaccine could be used alone or in combination with either the existing U.S. anthrax vaccine or the one being developed by the U.S. military.

"Either alone or in combination with existing vaccines, the data presented demonstrate that adenovirus-based vaccines represent a highly effective, safe, and inexpensive format that should be considered for future vaccine design," he said.

The vaccine needs to be tested in humans, although other studies suggest that this dose of adenovirus is safe in humans, according to Dr. Crystal. About 30 percent to 50 percent of people are already immune to the type of adenovirus used in the study, so it's not clear how this would affect vaccination, he said.

Drs. Yadi Tan, Neil Hackett, and Julie Boyer -- all of Weill Cornell Medical College -- were co-authors of the study.

Anthrax is caused by Bacillus anthracis, a spore-producing bacterium. If spores are introduced into the skin (cutaneous anthrax), lungs (inhalation anthrax), or intestine (gastrointestinal anthrax), they grow into bacteria that produce deadly toxins. Anthrax is a rare disease in the U.S. that is most commonly found in animals such as goats, cows, and sheep. Most people who contract the disease do so from handling infected animal products.

This work is funded by the National Institute of Allergy and Infectious Diseases/NIH Northeast Biodefense Center (1 U54 AI057158-01), as well as by a generous donation from the Robert and Renee Belfer Family Foundation.

For more information, or to contact Weill Medical College of Cornell University, see their website at: www.med.cornell.edu