New oral vaccine combats various versions of the plague

Jul 31 2008

A University of Central Florida researcher may have found a defense against the Black Plague, a disease that wiped out a third of Europe's population in the Middle Ages and which government agencies perceive as a terrorist threat today.

UCF Professor Henry Daniell and his team have developed a vaccine that early research shows is highly effective against the plague. Findings of his National Institutes of Health and USDA funded research appear in the August edition of Infection and Immunity. The vaccine, which is taken orally or by injection, was given to rats at UCF and the efficacy was evaluated by measuring immunity (antibody) developed in their blood.

All untreated rats died within three days while all orally immunized animals survived this challenge with no traces of the plague in their bodies. The rats were exposed to a heavy dose of Yersinia Pestis bacteria, which causes the plague, at the U.S. Army Medical Research Institute of Infectious Diseases in Maryland. It is one of a few labs in the world authorized to store and work with the highly dangerous agent.

"We are very excited because it appears the oral vaccine is even more effective than traditional injectable vaccine," Daniell said. "This could really make a difference."

In the event of a bioterror attack, the oral form makes the vaccine practical, as the distribution of pills would be much quicker and likely more effective because no special skills or sterile needles are needed to administer them.

"It worked beautifully," Daniell said. "It's expensive to create an injectible vaccine. But with oral vaccines, it is quite cheap. You grow your plants and then you convert them into capsules."

The plague had a deadly impact on early Europe, it continues to make appearances today in places like Africa and Asia. The World Health Organization reports at least 2,000 cases of the plague annually. The most recent outbreak in 2005 killed 56 people in the Congo and another 124 were infected before the epidemic was stopped. In the mid 1990s more than 400 people were infected in India.

Although human trials are still needed, Daniell is confident the vaccine will work for the bubonic and pneumonic plague based on animal studies. Pneumonic plague is spread through the air. Without treatment a person can die within days. Bubonic plague is the more common form and is transmitted through fleabites and kills about 70 percent of those infected within 4-7 days if not treated. It was the version that ravaged Europe. If the early findings hold true, this vaccine could mean an extra layer of protection against natural epidemics and man-made threats.

The Centers for Disease Control lists the pneumonic plague as a potential bioterrorism agent because of the speed of which it can be spread and its 60 percent fatality rate if not treated early enough with an aggressive array of antibiotics.

Daniell was inspired to investigate an oral vaccine for the plague because of his pioneering work in diabetes. He and his team genetically engineered tobacco and lettuce plants with the insulin gene and then administered freeze-dried plant cells to five-week-old diabetic mice for eight weeks. By the end of this study, the diabetic mice had normal blood and urine sugar levels, and their cells were producing normal levels of insulin.

Daniell figured the same approach might work with a vaccine. He genetically engineered plant cells with a protein found on the outside of Yersinia pestis. The vaccine was inside the plant cells, which were given to the rats. The vaccine was protected from digestion in the stomach and was then absorbed in the gut. It kick started the immune system into producing antibodies, which protects against the deadly disease. Three to five doses seem to do the trick.

Daniell, who was born and raised in India, has dedicated his life to finding treatments and cures to diseases that ravage poor countries. He is conducting research into seven of the top 10 diseases ranked by the World Health Organization and the Centers for Disease Control, which remain real issues developing nations.

"I've seen the need. There may be some very expensive treatments available," Daniell said. "But they are so expensive that developing countries can't access them. I want to help change that."