New Vaccine For Bovine Diarrhea Could Help Humans

As the scientists develop the vaccine for calves, their work could lead to advances in helping humans susceptible to the disease. Frequent travelers, children at day-care facilities, AIDS patients and other immune-suppressed people are especially at risk of contracting cryptosporidiosis and have difficulty shedding the infection.

Cryptosporidium parvum infects the intestinal tract of almost all mammals, but is most harmful in humans and cattle, says Dr. Lance Perryman, head of the department of microbiology, pathology and parasitology at NC State's College of Veterinary Medicine and lead investigator of a just-published study on the vaccine.

Because there are no approved drugs on the market that prevent or treat the infection, Perryman said, his team set out to determine what component of the immune system controls the infection and to develop a vaccine. The result was an immunization made of recombinant protein that can be administered to pregnant cows, whose bodies will produce the necessary antibodies. The mothers deliver the antibodies to newborns through colostrum -- the mothers' first milk.

In a research study published in the April 23 issue of the journal Vaccine, the NC State researchers reported that infected calves fed milk from vaccinated mothers did not develop cryptosporidiosis, as did infected calves that ingested milk from nonvaccinated mothers. The immune colostrum reduced by 99.8 percent the production of C. parvum oocysts -- the excreted form of the infectious agent.

The scientists hope the experiment's results will lead them in the right direction to find a vaccine for humans. "The biology of infection is very similar whether you're talking about humans or animals," Perryman says. "If we identify antigens that induce protective immune responses in one species, it's likely that those same antigens will induce protective immune responses in another species." Scientists should be able to use the same immunization strategies, but different sources of antibodies, he says.

NC State has applied for a patent on the vaccine for cattle and is in discussions with several companies about large-scale production.

The experiment's results, signifying successful prevention, will have a major impact on protecting the environment and the profitability of beef and dairy cattle, Perryman says. Cryptosporidiosis rarely results in death. The real problem is economic loss -- the result of an infected calf's slower growth rate and the expenditures on additional labor and rehydration fluids.

"In a beef cattle operation, an infected calf is smaller, grows slower, and doesn't convert feed as efficiently," Perryman says. "A dairy calf would grow a little slower and would be older when she began milking."

"Reducing environmental contamination by cryptosporidiosis is equally important," Perryman says. The disease is transmittable through oral and fecal contact and can be spread to humans from the water supply. Calves are easily infected when they come into contact with C. parvum on the ground. Perryman says the vaccine, which reduces the number of C. parvum oocysts excreted, should lower contamination levels.

To test the vaccine, Perryman, associate professor Dr. Elaine Hunt, and researchers Sushila Kapil and Michael Jones first identified a particular antigen triggered by C. parvum. Then, they cloned genes directing synthesis of the antigen and used the recombinant protein to stimulate production of the appropriate antibody.

Six cows in late stages of pregnancy received immunizations with the protein-laden vaccine, and six other pregnant cows served as the control group. The recombinant protein induced the cows to make antibodies, which were packaged within the colostrum, a rich source of maternal antibodies for all types of infection. Colostrum was collected from each cow and pooled into collections of immune colostrum and control colostrum.

Twelve unrelated newborn calves, divided equally into test and control groups, were challenged with highly infectious doses of C. parvum. In a blind administration, six calves received immune colostrum, and six received control colostrum. Without bias, technicians observed the health of the calves, measuring their total fecal volume and the amount of oocysts in the fecal material.

The control calves all had severe diarrhea, shedding an average of 8,447milliliters of fecal volume, more than 11 times as much as the calves fed immune colostrum. The immunized calves shed significantly fewer oocysts -- about three billion total compared to 1.87 trillion for non-immunized calves.

Perryman is part of another team of researchers, funded by the National Institutes of Health, working to develop treatment strategies for high-risk human populations. For persistently infected patients -- those with weakened immune systems -- the researchers want to deliver immune components to help them clear the infection.

"We've produced a variety of monoclonal antibodies in mice," Perryman says, "and we're in the process of testing them singly and in combinations to see if the oral administration of monoclonal antibodies might work to successfully treat infection." This work is still in animal model trials, he says.