Wednesday, October 4, 2023

Construction of a probiotic-based vaccine to protect against CD

By Dr. Denise Heard U.S. Poultry & Egg Association

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TUCKER, Ga. — Clostridial dermatitis (CD), commonly referred to as Gangrenous dermatitis, is caused by the anaerobic spore-forming Clostridium septicum and/or Clostridium perfringens type A.

It is an economically important emerging disease of turkeys and broiler chickens. The disease has been reported to affect about 40 to 50 percent of U.S. turkey grower farms, causing economic losses due to poor production rates and sudden spikes in mortality.

Clinically, CD is characterized by necrotic dermatitis with edema and/or emphysema in the underlying subcutaneous tissues and sudden death. The most significantly affected areas include breast, back, abdomen, thighs, tail and wings. A presumptive diagnosis of CD can be made based on history, clinical signs, and gross anatomic and microscopic lesions. However, confirmation should be based on demonstration of the causative agents by culture, polymerase chain reaction, immunohistochemistry, and/or fluorescent antibody tests.

Clostridial dermatitis was initially recognized for many years as a sporadic disease, but the prevalence and severity of this condition increased over the past two decades in the United States, especially in turkeys. Several managemental and environmental predisposing factors are implicated in the development of CD in turkeys. These include overcrowding, poor ventilation, inadequate hygiene, built-up/deep litter production systems and immunosuppression.

The disease pathogenesis is poorly understood, mainly because of its complexity and multifactorial characteristics, including virulence factors of the clostridial agents, flock management, disease predisposition and host immune status.

There are two notions which are currently acknowledged to describe the pathogenesis of CD. The first proposes the entry of the microbe from the intestine into circulation, reaching the skin.

Many Clostridial species are ubiquitous in nature, such that the noticeable disease is not apparent until stress or enteric infections induce intestinal inflammation resulting in gut leakage and, thus, allowing the passage of the pathogen into circulation. Upon reaching the circulation, the bacteria gains access to the sites of skin abrasions or hypoxia, where they can further multiply and produce toxins.

The second theory suggests the entry of the Clostridial pathogens into the subcutaneous tissues via skin wounds, where they multiply and secrete potent exotoxins, including the C. septicum alpha-toxin (ATX), with a resultant septicemia followed by sudden death.

Losses due to CD frequently result in poor production and deaths in the affected flocks and often require antibiotic intervention. To date, good management practices and antibiotics have been somewhat shown to reduce CD incidences but have failed to eliminate the disease.

Several CD control strategies in turkeys have been tried and tested with variable success. These include improved managemental practices such as reducing bird density, humidity control, feed microbial supplements (probiotics) and others. Vaccination is another approach that seemingly offers better success than others. However, for commercial poultry applications, parenteral immunization routes are unsuitable, and a practical vaccine delivery platform is needed to be of value to the industry.

During the spring 2021 USPOULTRY Research competition, Dr. Ravi Kulkarni and his research team at North Carolina State University received funding to develop a probiotic-based recombinant oral vectored-vaccine against Clostridial dermatitis. This funding was part of the USPOULTRY Board Research Initiative program aimed at addressing very specific and important issues affecting the industry.

The study proposes to clone and express the immunogenic domains of C. septicum ATX into Lactococcus vaccine vectors to develop an oral vaccine against CD in turkeys. The key feature of these vectors is that they are not only flexible for genetic manipulation but are also safe and possess probiotic properties in poultry. This added advantage can aid in outcompeting the enteric pathogenic clostridia, while expressing vaccine target proteins for optimal induction of immunity against the disease of interest.

The study design addresses three specific objectives over the course of three distinct experiments. Researchers will construct a recombinant Lactococcus–based vectored vaccine expressing C. septicum ATX domains to develop an oral CD vaccine.

Turkeys will be orally immunized with this vaccine to evaluate protection against CD using an in-house experimental C. septicum challenge model. Protection will be assessed by bird performance parameters and gross and histopathology of skin lesions. Finally, systemic, and local immunological mechanisms of protection against CD will be evaluated.

This work has the potential to provide sustainable value-added means for the industry to grow birds without relying much on antibiotics usage for CD control.


Dr. Denise Heard is director of research programs with the U.S. Poultry & Egg Association based in Tucker, Ga. She can be reached by e-mail at

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