POULTRY disease is an international issue, especially when there is an outbreak close to home. However, it's a particularly costly problem in developing countries.

Breeding animals to be resistant to disease may be one possible long-term solution. University of Georgia researchers in the Regenerative Bioscience Center have spent the last four years gathering data that could make the process a reality.

The team, which includes Steven Stice and Franklin West in the University of Georgia College of Agricultural & Environmental Sciences and Claudio Afonso at the Agricultural Research Service's Southeast Poultry Research Laboratory of the U.S. Department of Agriculture, used a technology platform called shRNA -- single strands of RNA that fold back on themselves -- to selectively stop the production of nucleic acids that cause disease, such as the Newcastle disease virus.

Newcastle disease is a worldwide problem and is caused by one of the most deadly of all viruses that spreads among birds. Exotic Newcastle virus, the most devastating form of the virus, has been eradicated in the U.S. and Canada. The milder forms of Newcastle are kept under control using vaccines.

The research team's tooling process for enhancing disease resistance, published recently in the Journal of the International Alliance for Biological Standardization, is potentially a much better way to protect against disease than vaccination because it introduces permanent genetic resistance, which is transmittable to a bird's offspring, the researchers said. In contrast, many vaccines provide protection for a given period of time and must be re-administered periodically.

"With this technology, we can target specific regions used by the Newcastle disease virus that are critical for its survival," said Stice, a Georgia Research Alliance eminent scholar and director of the Regenerative Bioscience Center. "Preventing these lethal viruses from replicating in individual chickens may, in the end, reduce the overall level of virus transmission from one chicken to the next."

Multiple types of animals and diseases could be targeted. This technology could also be applied to avian influenza and swine flu.

"Ultimately, you could have birds that are both avian influenza resistant and Newcastle disease virus resistant," said West, an assistant professor in the animal and dairy science department. "Theoretically, you may never have to vaccinate again."

Organized distribution of vaccine products can present problems, especially in countries where farmers may not have a refrigerator or other means to store the vaccines at the temperature needed to keep the vaccine alive. This is particularly true in rural areas, where backyard flocks may be a farmer's main source of income.

Shipping disease-resistant chickens produced in the U.S. could be the best possible solution for many countries, Stice said.

"We've taken many years to prove that this technology is viable, and we're now ready to expand our work to the next stage," he said.

Extra-virulent viruses

Scientific experiments with the herpesvirus that causes Marek's disease in poultry have confirmed, for the first time, a controversial theory that some vaccines could allow more virulent versions of a virus to survive, putting unvaccinated individuals at greater risk of severe illness.

The research has important implications for food chain security and food chain economics, as well as for other diseases that affect people and agricultural animals, according to an announcement from Pennsylvania State University.

"The challenge for the future is to identify other vaccines that also might allow more virulent versions of a virus to survive and possibly to become even more harmful," said Andrew Read, a leader of the research team whose paper describing the research was published in the scientific journal PLoS Biology.

"When a vaccine works perfectly, as do the childhood vaccines for smallpox, polio, mumps, rubella and measles, it prevents vaccinated individuals from being sickened by the disease, and it also prevents them from transmitting the virus to others," said Read, the Evan Pugh professor of biology and entomology and Eberly professor in biotechnology at Penn State.

These vaccines are dubbed "perfect" because they are designed to mimic the perfect immunity people naturally develop after having survived one of these diseases.

"Our research demonstrates that another vaccine type allows extremely virulent forms of a virus to survive -- like the one for Marek's disease in poultry, against which the poultry industry is heavily reliant on vaccination for disease control," said Venugopal Nair, who led the research team in the U.K., where the experimental work related to this study was carried out.

Nair is head of the Avian Viral Diseases program at the Pirbright Institute, which also hosts the World Organization for Animal Health Reference Laboratory on Marek's disease.

"These vaccines also allow the virulent virus to continue evolving precisely because they allow the vaccinated individuals and, therefore, themselves to survive," Nair said.

Less-than-perfect vaccines create a "leaky" barrier against the virus, so vaccinated individuals sometimes do get sick, but typically with less-virulent symptoms. Because the vaccinated individuals survive long enough to transmit the virus to others, the virus also is able to survive and to spread throughout a population.

"In our tests of the leaky Marek's disease virus in groups of vaccinated and unvaccinated chickens, the unvaccinated (birds) died, while those that were vaccinated survived and transmitted the virus to other birds left in contact with them," Nair said. "Our research demonstrates that the use of leaky vaccines can promote the evolution of nastier 'hot' viral strains that put unvaccinated individuals at greater risk."

The theory tested by the research team was highly controversial when it was first proposed more than a decade ago, but the team's experiments now show that the modern leaky vaccines widely used in poultry production, can have precisely the effect on the evolution of more virulent strains of the virus that the controversial theory predicted.

In the 1950s, Marek's disease was a minor disease that did not do much harm to chickens, but the virulence of the virus has evolved, and today, it is capable of killing all of the unvaccinated birds in a poultry flock, sometimes within 10 days.

"Even though the Marek's disease virus is much nastier now than it was in the 1950s, it is becoming increasingly rare, and now it causes relatively minor problems in the poultry industry because almost every chicken in agricultural production worldwide is vaccinated against the disease," Read said, explaining that if all the individuals in a population can be vaccinated against a virus, it does not matter if the virus has become super-virulent, so long as the vaccine continues to be effective.

The virus for Marek's disease is very virulent, but the virus causing avian influenza can be even worse.

"The most virulent strain of avian influenza now decimating poultry flocks worldwide can kill unvaccinated birds in just under three days," Read said, adding that the vaccine against avian influenza is a leaky vaccine.

"In the United States and Europe, the birds that get avian influenza are culled, so no further evolution of the virus is possible," Read said. However, "instead of controlling the disease by culling infected birds, farmers in Southeast Asia use vaccines that leak, so evolution of the avian influenza virus toward greater virulence could happen."

Gut health biomarkers

Alternative grains such as wheat, barley and rye that are high in non-starch polysaccharides (NSPs) can have a substantial negative effect on monogastric digestion and animal performance.

Chickens have little or no intrinsic enzymes capable of hydrolyzing these NSPs, leading to restricted digestibility of feed ingredients and significant reductions in growth. Undigested feed ingredients in the gut provide nutrients for bacteria overgrowth in the hind gut, which can lead to dysbacteriosis. High-NSP diets have also been associated with bacterial diseases that have major economic implications in broiler chickens.

In a recent research study titled "Identification of Potential Biomarkers for Gut Barrier Failure in Broiler Chickens," published in Frontiers in Veterinary Sciences, Novus International Inc. and University of Arkansas researchers used coccidiosis over-vaccination to trigger a gut health challenge in broiler chickens fed a wheat/barley/rye diet.

The overall growth performance and feed efficiency were severely reduced by this gut barrier failure model. The results of this study are in agreement with previous studies that concluded that high-NSP diets compromised growth performance in chickens, Novus said.

The purpose of the study was not to determine the individual effects of dietary ingredients or a coccidia challenge but, rather, to determine potential biomarkers that may be used to define gut barrier failure in future studies. Biomarkers could be useful for monitoring poultry health and understanding disease mechanisms.

Jeffery Escobar, executive manager of physiology research at Novus, said, "The results of this study will allow scientists at Novus, academia and other poultry researchers to perform better evaluations of gut health parameters and enhance the ability to test solutions, which can translate into safer poultry products for human consumption."

Volume:87 Issue:33