Gene Transfer Technique Immunizes Mice Within 12 Hours
Dec 29, 2004
In any bioterror attack, vaccines that provide a rapid, effective defense against the pathogen will be key to saving lives.
However, in the case of anthrax, vaccines available today can take weeks or even months to gain full effect.
Research underway at Weill Cornell Medical College in New York City may provide health officials with a much quicker option. Using gene transfer technology, investigators here were able to immunize mice against anthrax in just 12 hours.
"That's important, because in the event of an attack, those in charge won't necessarily know whether another attack is coming – or who might be affected. In that case, you want immunity to be built up in key populations as quickly as possible," said Dr. Ronald G. Crystal, Chairman of the Department of Genetic Medicine, Weill Cornell Medical College, and Chief of the Division of Pulmonary and Critical Care Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
His team's findings will be published in the February issue of Molecular Therapy.
According to Dr. Crystal, vaccines tend to fall into one of two groups – active vaccines, where the body is prompted over time to build up antibodies against specific threats; and passive vaccines, where fully-formed antibodies are delivered to the body in vaccine form.
"Because the body continues to produce antibodies, active vaccines last much longer than the passive kind, whose effectiveness tend to diminish over time," he explained.
But active vaccines have one major drawback: they need lots of time to develop. For example, the anthrax vaccine provided to U.S. Army troops following the 2001 attacks requires that troops receive six doses stretched over 18 months.
Populations threatened by the sudden dispersal of deadly anthrax spores won't have the luxury of that much time. So Dr. Crystal and his team turned their attention to faster-acting passive vaccines instead.
"We looked especially at the use of gene transfer technology – introducing genes that can manufacture antibodies against key components of the anthrax toxin," he said.
Genes need a live means of entering the body, however, so Dr. Crystal's team incorporated the gene within a harmless organism called an adenovirus.
Once inside the mouse's body, the gene began producing an immune-system antibody targeted to a key component of the deadly anthrax toxin.
"The adenovirus delivers the gene to the mouse, and then the gene goes to work – telling the animal's body to make this antibody against anthrax," Dr. Crystal said.
"Mice were immune to anthrax within 12 to 18 hours of vaccination," he said. "Compared to other vaccine technologies, this gene transfer strategy works very quickly."
While gene transfer has been used to deliver antibodies in other clinical settings, "to our knowledge this is the first time it's been used as a strategy against bioterrorism," Dr. Crystal said.
Of course, many hurdles remain before this type of vaccine might be ready for public use. Because humans are so much bigger than mice, dosing issues remain. It might also take two or more years of testing in animal models before the vaccine is deemed safe enough to test in humans.
Passive vaccines might never fully replace active varieties, Dr. Crystal said. In fact, the new vaccine will probably work best when used in combination with an active vaccine.
"Remember, passive vaccines like this one can lose their effectiveness over time, whereas active vaccines do not," Dr. Crystal explained. "We're now developing a strategy where we might give people both the active and passive vaccine. With the passive vaccine you'd get protection that would last a couple of weeks, but that would give you a safety margin while your body is developing more active, long-term immunity."
The research was supported, in part, by a Gift from Robert A. Belfer to Support Development of an Antibioterrorism Vaccine, and by the Will Rogers Memorial Fund (Los Angeles, CA).
Co-researchers included Dr. Kazuhiko Kasuya, Dr. Julie Boyer, and Dr. Yadi Tan of the Department of Genetic Medicine at Weill Cornell Medical College; and Dr. Neil R. Hackett and D. Olivier Alipui of the Belfer Gene Therapy Core Faculty at Weill Cornell.