Candidate fowl typhoid vaccine developed

Candidate fowl typhoid vaccine developed

- Modified salmonella strain produces robust immune response.

- Once response occurs, built-in mechanism disables virulence gene.

- Delayed-attenuation vaccines could have wide applicability.

CHICKENS are vulnerable to a range of infectious diseases such as fowl typhoid, a widespread and devastating illness, particularly in the developing world.

Now, Ken Roland and colleagues at the Arizona State University Biodesign Institute have developed a candidate vaccine to safeguard poultry from fowl typhoid infection while also providing protection against a related human bacterial strain: Salmonella enteritidis.

"Fowl typhoid, caused by Salmonella gallinarum, an avian-specific pathogen, accounts for about 10% of mortality of chickens in the developing world, although this disease is often underreported," Roland explained.

The group's approach to immunization relies on a modified strain of S. gallinarum that produces a robust immune response in Rhode Island Red chickens similar to the response produced by the naturally occurring pathogen.

However, once a strong, system-wide immune response has been elicited, a built-in mechanism disables the gene responsible for bacterial virulence, an announcement from the Biodesign Institute said. The technique provides better protection from fowl typhoid compared with existing vaccines while also offering an increased level of safety.

The group's research results appeared in the journal Vaccine.

S. gallinarum attacks birds of all ages, particularly broiler parents and brown-shell egg layers, the announcement said.

While chickens are most commonly affected, the disease can also infect many other types of birds, including turkeys, game birds, bullfinches, guinea fowls, sparrows, parrots and canaries. Fowl typhoid is responsible for widespread morbidity and mortality in poultry, particularly in Africa, Asia, Europe and Latin America.

"In many developing countries, chickens represent far more than just a food source, although (poultry) is typically the primary source of animal protein," Roland said. "The free-range flock scenario exposes these birds to diseases carried by the wild bird population, which includes fowl typhoid. Increasing the quality and productivity of backyard chickens will, thus, provide an immediate impact on the quality of life of the rural poor."

Morbidity from fowl typhoid ranges from 10% to 100% in stressed or immunocompromised flocks. Birds typically acquire the infection through fecal-oral contamination or via the navel/yolk. The bacterium is fairly hearty, resistant to changes in climate and capable of surviving for months.

Birds infected with S. gallinarum typically display a variety of symptoms, including lack of appetite, dejection, ruffled feathers, thirst, yellow diarrhea and a reluctance to move.

In attempting to combat such illnesses, various vaccine strategies have been developed. Live vaccines using weakened or attenuated salmonella strains provide greater levels of protection than killed injectable vaccines by engaging all three branches of the immune defense -- provoking humoral, mucosal and cell-mediated immunity -- which is important for clearing salmonella infections, Roland pointed out.

Nevertheless, it remains a challenge for vaccinologists like Roland to create vaccines that retain strong immunogenicity once they have been attenuated to ensure safety and reduce harmful reactions in the host. In the case of existing fowl typhoid vaccines, full protection typically requires multiple injections, making it cost-prohibitive in much of the developing world. Further, the vaccine is virulent in some birds.

Roland and his colleagues have instead produced a single-dose oral vaccine. The experimental vaccine strains in the current study make use of a technique known as delayed attenuation, which was developed in the laboratory of Roy Curtiss, who directs the Biodesign Institute's Center for Infectious Diseases & Vaccinology.

With delayed attenuation, the salmonella strain enters the system with its native virulence intact, producing a strong, systemic immune response. Then, a key virulence-related gene switches off after a number of cell divisions, thereby shutting down the bacterium's disease-causing potential.

The trick in delayed attenuation is to re-engineer the salmonella virulence gene so that it requires the artificial sugar arabinose for effective functioning, Roland said. Once the bacterial cell's storehouse of arabinose is exhausted, the virulence gene essentially short-circuits and becomes inactive.

The study indicates that delayed-attenuation salmonella vaccines can have wide applicability for effective protection against a range of infectious diseases.

In future efforts, the group hopes to fine-tune a vaccine strain with more than one attenuating mutation, at least one of which remains unaffected by dietary components, thereby offering improved safety along with maximum immunogenicity.

"Our goal is to utilize 'high-tech' strategies to provide a 'low-tech,' easy-to-use, inexpensive vaccine, allowing everyone from backyard farmers to commercial hatcheries to vaccinate their flocks, resulting in better food security in the developing world," Roland said.

Volume:85 Issue:10

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