Lettuce, new source for our future vaccines

It started more than 200 years ago with cowpox, a weak cousin to the deadly smallpox virus. Doctors purposely infected people with the cow disease to protect them from the scourge. Centuries later, the basic concept behind vaccines has not changed. Most are versions of the very bacteria or viruses that we want to avoid. Henry Daniell thinks there is a better way. The University of Central Florida researcher is working on a new kind of vaccine that is grown inside plant cells, crushed into powder and swallowed as a capsule. He recently had success in animal tests of his vaccine for bubonic plague. "What we have developed is a totally new platform; it's a revolutionary approach," said Daniell, who receives funding from the National Institutes of Health and others for his research.

Vaccines, often given as shots, work by stimulating the body's natural defenses. The immune system attacks the invader and becomes resilient to future infections. Vaccines have tamed many diseases that once killed and maimed indiscriminately, such as measles, diphtheria and polio. But most are expensive and hard to manufacture. In rare cases, the vaccines themselves cause the disease or severe reactions. That's why Daniell and others are working on new types that reduce the risks and expense. The need has become more urgent in recent years amid fear of bioterrorism and natural outbreaks such as bird flu. Daniell's approach relies on selected genes from the bacteria or viruses — not the whole pathogens. At a basic level, genes are the recipes for proteins. Researchers have found that the immune system can be provoked by just a few proteins from the invader. Consider the experimental vaccine for bubonic plague. Though uncommon today, the plague has killed millions throughout history to earn its nickname: the Black Death. There are still cases every year in parts of Africa and Asia.

In the United States, health officials are more concerned about plague as a weapon of bioterrorism. That's why Daniell was able to get the U.S. Army to help with his recent tests on mice. In creating the vaccine, Daniell chose a few genes from the plague bacteria and spliced them into the genetic blueprint for lettuce. Then he grew the genetically modified plants. Because they hold the genes, the lettuce also creates the proteins that could rev up the immune system.

Some of the mice ate a compound of the crushed lettuce leaves. Others received injections of another plague vaccine. The rest of the animals were not immunized at all. Then Army researchers exposed the animals to the dangerous bacteria. The mice that took Daniell's oral vaccine survived. But all of the non-immunized animals died, along with most of the mice that had the injectable vaccine. Daniell and his colleagues published the results of the test in the August edition of the journal Infection and Immunity.

"What we're seeing here is that the oral vaccine can be very effective," said Daniell, a UCF professor of molecular biology. "It's also a very cheap way to create a vaccine — by altering plant cells and creating a pill. If you have to vaccinate millions of people in a bioattack, it's much easier to hand them a pill than to give out shots." He is among only a few vaccine researchers worldwide using lettuce, though others are experimenting with potatoes and different food crops. Daniell said he is focusing on the plant because it is inexpensive and easy to grow. His lab uses an ordinary variety of lettuce similar to what you might find on your salad plate.

"Lettuce is eaten almost everywhere in the world. It's very common, and it's very feasible to modify it genetically," Daniell said. "Plus, it produces nice, green leaves that lend themselves to drying and powdering."

Sound too good to be true? For now, it is.

Many hurdles remain for vaccines based on the genetic components of disease-causing pathogens, said Darren Higgins, an associate professor of microbiology and immunology at Harvard University. For starters, scientists don't always know what genes are sufficient to provoke an immune response, Higgins said. Then they still have to find ways — such as the lettuce leaves — to give people just the right dose of DNA or its proteins.

"The issue is how do you deliver it in a way that's going to be effective and yet where you're not going to have any toxicity," said Higgins, also a founder of a biotechnology company that is working on the approach.

Daniell said his team has had success in tests of similar vaccines for malaria and cholera. He thinks it's just a matter of time before it's refined.

"I am confident this platform will be validated and someday, people will have the opportunity to get cheap and effective vaccines," he said. via Herald Leader.

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