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VMRCVM researchers develop swine vaccine

By Jeff Douglas

Spectrum Volume 17 Issue 18 - February 2, 1995

Microbiologists in the Virginia-Maryland Regional College of Veterinary Medicine have developed the first live attenuated vaccine for swine pleuropneumonia, one of the most important infectious disease problems faced by pork producers and the most common bacterial swine respiratory disease in the world.

The live attenuated vaccine confers a comprehensive, long-lasting protective immunity in vaccinated animals, yet does not cause disease, according to microbiologist Thomas Inzana.

The researchers have also created a diagnostic test that can detect swine pleuropneumonia with 98-percent sensitivity and 97-percent specificity using a simple nasal swab.

Caused by an organism called Actinobacillus pleuropneumoniae, swine pleuropneumonia can devastate swine herds and is believed to account for millions of dollars a year in production losses. Victims develop pulmonary lesions, fibrinous adhesions, and pneumonia.

Until now, producers have been forced to use less effective killed vaccines that reduce animal mortality, yet fail to control clinical and sub-clinical infections responsible for diminished weight gain, poor performance, and a carrier state.

Since the days of Pasteur, medical researchers have been working on the development of new and improved live vaccines to protect people and animals from many disease-causing bacterial and viral pathogens.

"The immune response is very complicated," said Inzana, who conducted much of the research in conjunction with grants from the USDA, the National Pork Producers Council, and Virginia's Center for Innovative Technology. "It is a vast network that is not fully understood."

What is understood, however, has enabled scientists to make remarkable progress in quelling a variety of diseases that threaten human health and well-being and agricultural animal productivity.

Traditional killed vaccines--created by killing an infectious agent with formalin or heat, mixing it with an adjuvant to enhance the immune response, and then injecting it into a person or animal to stimulate immunity--may provide an acceptable immune response, but cause troublesome side-effects such as inflammation.

The white blood cells that flock to the site of an invading pathogenic organism create an inflammatory response that can be damaging in itself. The goal of modern immunology is to develop immunogenic agents that are so precise they minimize the body's inflammatory response while promoting maximum protection.

Recent advances in molecular biology have enabled researchers to create genetically altered live vaccines that provide a more comprehensive and long-lasting immunity, yet do not cause disease in the host, according to Inzana, who worked closely with pathologist Hugo Veit on the project.

Researchers know the best immune response is elicited by natural exposure to the organism that causes the infection. Since it is not practical, however, to risk disease, Inzana and colleagues sought to identify and eliminate one or more of the organism's components responsible for virulence.

"The key is knowing which components of the organism the host needs to make a response to," said Inzana, who has recently been awarded more than $300,000 in new grants to continue his research.

Actinobacillus pleuropnemoniae, like many pathogenic bacteria, is covered with a carbohydrate capsule or shield, which helps protect it from the host's immune system. Inside these gram-negative bacteria are endotoxins that export potent exotoxins which damage tissues, induce inflammation, and cause the disease.

With the goal of devising a live-vaccine that would confer broad and enduring immunity without the pathogenic effects, Inzana used a mutagenic agent to inactivate the organism's DNA that encodes proteins for the export and manufacture of capsule, and then selected those bacteria that lacked capsule. Without the capsule, the bacteria cannot survive in the lungs or blood, but do induce a protective immune response after vaccination.

"We believe this technique will be effective for developing vaccines against any bacterium that produces extra-cellular toxins and produces a capsule," he said, including Pasteurella multocida and Pasteurella hemolytica--organisms that cause shipping fever in cattle.

A pharmaceutical company is developing a commercial vaccine based on Inzana's work.