"A toxoid is a molecule that's still able to produce an immune response but is no longer capable of causing disease."
DR. JOAN SCHRADER

In response to increasing consumer and regulatory pressures to get drugs out of the food chain, broiler companies are reducing or even eliminating antibiotics and growth promoters. In doing so, many are attracting new customers willing to pay a premium for antibiotic-free birds. But, without drugs on board to protect their flocks, producers are beginning to see serious economic losses from necrotic enteritis.

At least one animal health company has recognized the need for alternatives to managing necrotic enteritis and has been working feverishly to come up with an innovative solution.

Dr. Joan S. Schrader, a research scientist for Schering-Plough Animal Health, told symposium attendees about a novel new vaccine specially designed to combat necrotic enteritis in poultry. She also gave them an overview of some of the trials leading up to the vaccine's conditional approval by USDA, which regulates biological products.

The product is currently known as Clostridium perfringens type A toxoid. She explained that Schering-Plough Animal Health has already met the regulatory agency's criteria for bird, human and environmental safety. Full license will be granted pending the outcome of efficacy trials, which are currently under way. In the meantime, many producers are already using the Clostridium perfringens type A toxoid to manage necrotic enteritis in broilers.

New vaccine builds on earlier work in other species

Shrader noted that Schering-Plough is hardly a newcomer in the development of clostridial vaccines. "The company began manufacture of clostridial vaccines for animals in the 1960s, so now we now have more than 40 years of experience in developing clostridial vaccines for cattle and sheep," she reported.

As she sees it, the new vaccine for poultry is just a natural extension of that previous work.

Figure 1. Incidence of necrotic enteritis was significantly lower in all of the vaccinated groups.

Schrader, who served as the lead scientist on the project, said that she and her team tested numerous vaccine candidates before coming up with a suitable formulation. She said that clostridial disease in poultry is caused by the alpha toxin that is produced by Clostridium perfringens types A and C. Type A is by far the more common of the two, accounting for more than 95% of NE in poultry.

"The new vaccine is made from C. perfringens type A's alpha toxin that is inactivated into a toxoid," she added. "A toxoid is a molecule that's still able to produce an immune response but is no longer capable of causing disease."

Progeny protected by passive immunity

The NE toxoid is administered to hens at 10 to 15 weeks of age, then again at 17 to 20 weeks of age. It triggers antibody titers against the alpha toxin. Those antibodies are then transferred to the hen's progeny - a process known as passive immunity.

To find out how long immunity lasts in vaccinated hens, Schrader and her team undertook a series of studies. They vaccinated the hens once, then followed that with the booster a few weeks later.

Then they monitored the birds through the onset of lay, collected eggs during the early, mid and later portions of the laying cycle, and tested both the sera and egg yolks from the hens for antibody to the alpha toxin. Results from those studies were compared with controls.

"We had no titer in the sera of hens that were not vaccinated, but in the vaccinated hens, we had significantly higher titers, both at 35 weeks of age, then again when we re-tested them at 55 weeks," she said. "We tested egg yolks at 33 weeks of hen age, and 78 weeks of hen age, and we had significant titers out to 78 weeks of age."

Encouraged by those results, Schrader's team took the next step and tested the progeny of the hens. They set the eggs, hatched the chicks, and then fed the young birds a high-protein fishmeal diet designed to irritate the gut, which can promote necrotic enteritis. The birds were then challenged with C. perfringens type A on 3 consecutive days—19, 20, and 21—and then necropsied on days 22 and 23.

"We found that the incidence of necrotic enteritis was significantly lower in all of the vaccinated groups as compared to the control groups," she reported. "And that was in chicks that were hatched from hens that were 32, 52 and 65 weeks of age. (Figure 1)"

The researchers also compared necrotic enteritis lesion scores for vaccinated vs. control progeny and found that vaccinated birds had significantly lower scores than did controls.

Summing up her presentation, Schrader said the NE toxoid induced a significant antibody response in the sera of hens administered the vaccine and that those antibodies persisted through 78 weeks of age. Eggs from the vaccinated hens showed significant antibody titers through 65 weeks of age.

"We also found that that the NE toxoid produced no tissue reactions at the injection sites, was found safe when used under field conditions and, most importantly, the progeny of the hens vaccinated with the NE toxoid were protected from necrotic enteritis challenge," she said.

Spring 2008

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