Solving an avian scourge could also provide benefits to human health

[Source: Arizona State University] - The old adage ‘a bird in hand is worth two in the bush’ may very well apply to a new vaccine project underway in the lab of ASU School of Life Sciences Professor Roy Curtiss, director of the Center for Infectious Diseases and Vaccinology at the Biodesign Institute.

There, associate research scientist Melha Mellata is leading a USDA funded project to identify targets to develop a vaccine against a leading poultry disease, called avian pathogenic E. coli (APEC).

Mellata is an expert on understanding the genetic signposts of how certain kinds of E. coli turn deadly. “We have to understand how bacteria cause disease so that we can know the best way to fight them,” said Mellata.

According to the USDA, the two most common types of poultry infections are from the bacteria E. coli and Salmonella. Unlike in people, Salmonella is completely harmless to chickens.

But by attempting to solve the poultry scourge of APEC, Mellata and Curtiss are hopeful their ‘bird in hand’ project could ultimately provide a boost to protecting people against Salmonella, the leading cause of food-borne illness.

“What if you could get one vaccine to fight against a group of bacteria?” said Mellata. “We came up with a project where we would protect chickens, not only from E. coli infection but also Salmonella, and in doing so, improve human health.”

The U.S. has the leading poultry industry in the world, with an annual value of more than $50 billion and a poultry production forecast to continue its upward trend. E. coli infections are a big threat for the industry. The economic losses due to E. coli infections in broiler chickens were estimated to be more than $80 million in 2002.

Now, there is also considerable concern in the scientific community that APEC strains could become an emergent food pathogen. The poultry products are also a suspected source of a suite of infections called ExPEC (extra-intestinal pathogenic E. coli, which includes APEC), which have been associated with illnesses such as urethral infections, sepsis and meningitis.

Another human health ramification comes from work done by several research groups that have demonstrated that the poultry disease is also similar to other harmful E. coli, including the dreaded E. coli (O157:H7), which is responsible for human illness and death, typically from eating contaminated meat.

Antibiotics have long been the first line of defense to prevent APEC, but have lost their potency, as the bacteria have grown increasingly resistant to treatment.

“It’s becoming increasingly important to develop a vaccine to prevent bacterial infection in poultry,” said Mellata. “Poultry is not only a daily food staple, but less commonly known, also a key to human health. For example, the entire supply of flu vaccine production is made from eggs.”

Bacterial contamination resulted in half the U.S. flu vaccine supply being destroyed in 2004.

The difficulty in making a vaccine against Salmonella and E. coli is related to their genetic diversity. If the Curtiss research team is to be successful, the vaccine must be effective against a broad spectrum of E. coli and Salmonella groups.

In the past decade several researchers and commercial enterprises have developed Salmonella vaccines for animal health, but they are only effective against a few strains.

The Curtiss group has been a world leader in Salmonella-based vaccines. Curtiss’ international team alone has already developed two vaccines that are effective against Salmonella in livestock. By freeing animals from Salmonella, the vaccine is designed to prevent it from traveling down the food chain to people. His vaccine has received FDA approval for use with swine and poultry and is on the market.

The first step in vaccine development is to understand the molecular tricks bacteria use to elude a host’s immune system. Within the haystack of the E. coli bacterial genome, the research team has been focused on identifying the genes responsible for triggering its harmful effects.

But in order for the APEC vaccine to pull double duty, they must also demonstrate effectiveness against Salmonella. A key challenge of the project is to see if there is a common thread that can be found in E. coli and Salmonella-which genetically, are very distant cousins at best.

“The problem right now is understanding the virulence of APEC as well as Salmonella to find a way that will protect against all types of the bacteria,” said Mellata.

For the past generation, Curtiss has employed Salmonella as a Trojan horse against a variety of harmful pathogens. By using a similar approach, his team is currently developing a vaccine against bacterial pneumonia in a $15 million project funded primarily by the Bill and Melinda Gates Foundation.

For the USDA project, the APEC genes would be shuttled into the Salmonella bacteria in the hopes of triggering a protective immune response against both Salmonella and E. coli.

Mellata feels her team has many APEC gene targets they will use, and they are hard at work to identify several promising factors. The team hopes to have several candidates to test at the end of the three-year, $400,000 project, which will be completed in 2010.