Cuisine – or Vaccine? That Fruit May Be Both

By Corydon Ireland
May 8, 2000
Democrat and Chronicle
Rochester, NY

Afraid of getting shots?

Within a decade, patients worldwide might be able to eat genetically modified bananas to get their vaccinations, the medications that prompt the immune system to fend off serious disease.

The University of Rochester has a part in the basic research into edible vaccines, an investigation led for nearly a decade by Cornell University plant scientists.

UR's role-supplying genetic material to spur vaccine production in plants-is just part of the $11 million the university will spend this year on vaccine-related research. Other UR vaccine work includes look. ing into medicines that could one day prevent HIV, adult whopping cough and the widespread virus that causes genital warts and most cervical cancers.

Oral vaccines are already common. But edible vaccines would actually be grown within genetically en-gineered fruits or vegetables.

"This is going to be of greatest benefit in the developing world," said Dr. Robert Rose, a UR researcher helping to create and test edible vaccines.

In remote, poor countries, he said, such medicines would be produced locally -in bananas, potatoes or the leaves of tomatoes or tobacco.

How such crops would be regulated is a matter for future debate.

Edible vaccines will cut out the need for sterile equipment, trained medical personnel, refrigeration and costly distribution systems.

Cornell researchers are now busy trying to identify the best plant for vaccine production and delivery. Candidates include potatoes and the seeds of cereal crops and legumes. But Cornell's present focus is bananas, a familiar, palatable food and the best technical hope for "the fruit expression of antigens ' the particles that provoke that protective immune response.

Scientists there estimate that about 10 doses of vaccine—about one-third of an ounce each—would fit into a small baby food jar of mashed banana. UR's role in the Cornell-led research involves com-ing up with the genes that prompt a vaccinelike response in the im-mune system.

Genes carry the information for making proteins. Ant if you can find out what protein provokes a protec-tive immune response, you have the genetic key to making vaccines.

The target gene can be snipped out of human chromosomes and replicated by the millions in spe-cialized insect cells. "We get huge numbers of just the gene we're af-ter," said Rose.

In the Cornell work, the same vaccine gene is put into the genome of a plant. Once eaten, researchers hope, the plant food will provoke the same immune response that a normal vaccine would.

The genes are inserted into leaf cells. Boosted with hormones, those leaf cells become the shoots and roots that grow into full plants.

As early as this summer, Rose and other UR researchers will test a Cornell edible vaccine on mice.

Beginning with basics

Vaccines stimulate the immune system to fight off a specific disease. They use weakened or dead parti-cles of a virus or bacteria, which trick the body into creating anti-bodies against the invader.

So any vaccine research begins with basic research into the immune system.

"We try to understand basic pieces of the immune system, using disease models:' said Dr. Tim Mosmann, di-rector of UR's new Center for Vaccine Biology and Immunology. "It's not about solving the disease, but about finding out how it works."

The human immune system has a lot of mechanisms that come to bear when an infection strikes.

These include antibodies, special blood proteins that attack substances the body regards as foreign and po-tentially dangerous; and lympho-cytes, a family of white blood cells that kill virus-infected cells directly.

All these natural mechanisms, if prompted unnecessarily, can cause a lot of damage—"friendly fire:' said Mosmann, whose work on special-ized lymphocytes earned him several nominations for the Nobel Prize.

Antibodies running amok, for in-stance, are thought to cause rheumatic fever, pernicious anemia, rheumatoid arthritis and other au-toimmune diseases.

So part of UR's basic research re-lated to vaccines means looking at careful ways to regulate the mech-anisms that awaken the immune system. It's a major theme at five of seven laboratories at the UR vaccine center.

Other basic research themes:

• Looking into "vaccine mem-ory," the length of time antibodies stay potent enough to ward off dis-ease.

• Investigating the chemical sig-nals that turn down immune re-sponse. If such a response is too en-thusiastic, it can add up to the body attacking itself

• Looking into spurring immune response by injecting DNA into the body.

Another avenue of basic vaccine research is under way at the UR Cancer Center.

Cancer "vaccines" would not pre-vent disease, but would slow the ef-fects of cancers once they are pre-sent. "In cancer, the name of the game is still therapeutic:' said Dr. Joseph D. Rosenblatt, associate di-rector for clinical research at the center.

He and others are working on ways to deliver immune-stimulating molecules to the site of a tumor. Cancers of the breast, lymph nodes, skin and prostate are the major themes of this basic research.

Only one UR cancer vaccine— for melanoma—has reached the human trial stage, said Rosenblatt.

1-2-3 testing

Basic research can suggest new ways to deliver vaccines. But once a concept is in hand, clinical trials —bet inning with cultures, then progressing to animals and humans —have to show the medicines are safe and effective.

"We've established ourselves as one of the premier centers for vac-cine trials," said Dr. John Treanor, who directs UR's clinical vaccine trials for infectious diseases other than AIDS.

At any given time, he said, four to six human vaccine trials are be-ing done at UR, involving up to 500 volunteers.

A major study theme is flu vac-cines, especially those delivered by nasal spray.