Using gene transfer technology, investigators were able to immunize mice against anthrax in just 12 hours, according to new research featured in the February 2005 issue of Molecular Therapy, the peer-reviewed scientific journal of the American Society of Gene Therapy (ASGT).
In any bioterror attack, vaccines that provide a rapid, effective defense against the pathogen will be key to saving lives. Research underway at Weill Cornell Medical College in New York City may provide health officials with a much quicker option than vaccines currently available, which can take weeks or months to gain full effect.
"This research is important, because in the event of an attack, it may not be known 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.
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 tends to diminish over time," Dr. Crystal explained.
But active vaccines have one major drawback: they need lots of time to develop. For example, the anthrax vaccine provided to US 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 Cornell researchers turned their attention to faster-acting passive vaccines.
"We looked especially at the use of gene transfer technology -- introducing genes that can manufacture antibodies against key components of the anthrax toxin."
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.
"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.
The study found:
- Once inside the mouse's body, the gene began producing an immune-system antibody targeted to a key component of the deadly anthrax toxin.
- Mice were immune to anthrax within 12 to 18 hours of vaccination, indicating that the gene transfer strategy works very quickly.
- Passive vaccines might never fully replace active varieties. According to the research, the new vaccine will probably work best when used in combination with an active vaccine.
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.
Many hurdles remain before this type of vaccine might be ready for public use. Dosing issues will be an area of focus. 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 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 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; and Dr. Neil R. Hackett and D. Olivier Alipui, of the Belfer Gene Therapy Core Faculty, at Weill Medical College of Cornell University.