August 8, 1998 DNA vaccines for rabies, rotavirus advance
By N. Seppa
The newest vaccine technology has moved a step closer to benefiting some of the world's poorest people. Two studies of animals show that inexpensive and durable DNA vaccines work well against rabies and viral diarrheadiseases that hit developing countries hardest.
"This shows us that a new generation of vaccine technology is working its way forward," says Bruce G. Gellin, an epidemiologist at Vanderbilt University in Nashville, Tenn. DNA vaccines deliver genetic material encoding compounds designed to alert the immune system to an invading virus.
Although a preventive human vaccine against rabies exists, it is expensive and so is usually given only to veterinarians and researchers working with animals.
Scientists at Rocky Mountain Laboratories in Hamilton, Mont., which is part of the National Institute of Allergy and Infectious Diseases, have now developed a DNA vaccine at a fraction of the current vaccine's cost. The DNA encodes a glycoprotein found on the rabies virus. In a test on 12 cynomolgus monkeys, the DNA vaccine proved as effective as the commercial one.
Eight monkeys received the new vaccine, two were given the standard vaccine, and two remained unvaccinated. After initial vaccination, the two with the standard vaccination showed higher antibody levels than the DNA vaccine group. After a booster shot 6 months later, all those receiving either of the vaccines showed stronger immunity, the researchers report in the August Nature Medicine.
Seven months after the booster, the monkeys were infected with rabies. All 10 of those that had been vaccinated survived; the two controls died.
Six of the eight monkeys getting the DNA vaccine produced more antibodies than the two getting the commercial vaccine, study coauthor Donald L. Lodmell, a virologist at Rocky Mountain Laboratories says.
"This immune response is telling us that the animals were very well primed," Lodmell says. "When challenged with the virus, there was a tremendous response."
Although only a handful of people have died of rabies in recent years in the United States, the disease kills more than 40,000 worldwide annually. Uncontrolled outbreaks of rabies still occur in Asia and Africa, where the virus is endemic in places.
"We're primarily looking at [the DNA vaccine] as a prophylaxisgetting the vaccine into a large population," particularly people who don't have access to any treatment, Lodmell says.
A person exposed to the virus by an animal bite now gets a series of injections of vaccine and often several doses of antibody-creating immunoglobulin. This treatment doesn't work after symptoms have appeared. By that time, the disease is nearly always fatal.
Life-saving treatment for rabies in the United States can cost $1,000 per person, says study coauthor Charles E. Rupprecht, a microbiologist at the Centers for Disease Control and Prevention in Atlanta. Even pre-exposure vaccination costs as much as $400.
By contrast, the DNA vaccine could be provided for as little as 5 to 10 cents a shot, Lodmell says. Even if the commercial cost were 10 times greater, "that would still be orders of magnitude cheaper than the currently available vaccine," Rupprecht says. Moreover, the DNA vaccine "is very stable . . . and doesn't get denatured by heat," he says.
That attribute of DNA vaccines is also valuable in the fight against rotavirus. This virus causes diarrhea that kills almost 900,000 children every year, most in developing countries. While an injectible, traditional vaccine against the virus exists, the new rotavirus DNA vaccine is both edible and durable, making it the first oral DNA vaccine, the researchers contend.
When tested in mice, the encapsulated vaccine survived a trip through the animal's stomach and unleashed its DNA in the intestines or bloodstream, researchers report in the July Journal of Virology. Absorbed into cells, the DNA directs production of proteins that spur an immune response to rotavirus.
"Next, we'll try to do this in veterinary animals, such as pigs and cows," says study coauthor John E. Herrmann, a virologist at the University of Massachusetts Medical School in Worcester.
Both vaccines are inexpensive and resistant to tropical weather, attributes that "can greatly simplify vaccine delivery to the hardest parts of the planet to reach," Gellin says. Having an edible vaccine further simplifies logistics.
"As more people work with [the DNA vaccine technology], increasing its efficiency, it's really going to be a primary method of vaccination for the future," says Harriet L. Robinson of the Yerkes Primate Research Center at Emory University in Atlanta.From Science News, Vol. 154, No. 6, August 8, 1998, p. 85.
Copyright © 1998 by Science Service.
Chen, S.C. . . . J.E. Herrmann. 1998. Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles. Journal of Virology 72(July):5757.
Lodmell, D.L. . . . C.E. Rupprecht. 1998. DNA immunization protects nonhuman primates against rabies virus. Nature Medicine(August):949.
Debbie, J.G., and C.V. Trimarchi. 1997. Prophylaxis for suspected exposure to bat rabies. Lancet 350(Dec. 20):1790.
Fackelmann, K.A. 1997. Vaccine shields chimps from HIV. Science News 151(May 17):309.
Fishbein, D.B., and L.E. Robinson. 1993. Rabies. New England Journal of Medicine 329(Nov. 25):1632.
Sternberg, S. 1997. Hidden worlds collide. Science News 151(Feb. 8):94.
Travis, J. 1996. Swallowing shigella. Science News 149(May 11):302.
Bruce G. Gellin
Vanderbilt University Medical Center
Department of Preventive Medicine
Nashville, TN 37232-2637
John E. Herrmann
University of Massachusetts Medical School
Division of Infectious Diseases and Immunology
55 Lake Avenue, North
Worcester, MA 01655
Donald L. Lodmell
National Institute of Allergy and Infectious Diseases
Rocky Mountain Laboratories
Laboratory of Persistent Viral Diseases
Hamilton, MT 59840
Harriet L. Robinson
Yerkes Primate Research Center
924 Gatewood N.E.
Atlanta, GA 30329
Charles E. Rupprecht
Centers for Disease Control and Prevention
National Center for Infectious Diseases
Division of Viral and Rickettsial Diseases
Viral and Rickettsial Zoonoses Branch
Atlanta, GA 30333
copyright 1998 ScienceService