HBV Vaccines in Edible Plants Under Study

BUFFALO, NY--Vaccines in bananas? The idea may not be farfetched, as researchers at the Roswell Park Cancer Institute have successfully tested transgenic plants that express a hepatitis B virus (HBV) antigen.

HBV infection is the leading cause of liver cancer and is epidemic in developing third-world countries. It is estimated that 300 million people are carriers of HBV worldwide. While an effective HBV vaccine exists, it is expensive, requires refrigeration to maintain its potency, and must be given in three needle injections over a 6-month period.

"Global immunization programs are more difficult with vaccines that require a ‘cold chain’ or multiple inoculations," said Yasmin Thanavala, PhD, Molecular Immunology, Roswell Park.

Her laboratory is trying to find a way to make vaccines that can be shipped easily, kept fresh without refrigeration, and made affordable for countries where HBV is endemic. "While our ultimate goal is the banana, we have had success using the potato," she said at the first meeting of the Regional Cancer Center Consortium for Biological Therapy of Cancer, hosted by Roswell Park.

In pilot studies, researchers placed DNA from the hepatitis B virus into tobacco leaves by infecting the leaves with Agrobacterium containing the hepatitis B surface antigen (HBsAg) gene. The bacteria transferred the gene to the plant where it was incorporated into the DNA of the plant itself.

Much is known about the tobacco leaf, making it useful for testing purposes, Dr. Thanavala said. Thus, she and her colleagues used the tobacco leaf in their first experiments to establish proof of concept that plants are capable of expressing viral antigen, and, if expressed, the immune system will recognize the antigen.

These tests showed indeed that plants could take up an antigen and create a product that would elicit an immune response when injected into mice. The researchers then moved on to an edible plant--the potato.

Potatoes were transgenically altered (by Dr. Charles Arntzen of the Institute for Plant Research, Ithaca, NY) to express the HBsAg gene. Dr. Thanavala tested the immune function of the potatoes by feeding them to mice. Each mouse was fed 5 g of potato containing roughly 5.5 µg of HBsAg.

When the observed immune response to HBsAg declined, the mice were challenged with 0.5 µg of a commercially purchased vaccine. All of the mice had seroconverted and responded to the challenge by making a secondary immune response.

"While it was encouraging to see that the potato could also be used to create an appropriate immune response, very few people eat their potatoes raw. We tested the potatoes after they were boiled and found that boiling did decrease the efficacy substantially, although we could generate a reduced response to the cooked potato," Dr. Thanavala said.

The goal now for Dr. Thanavala’s lab is to recreate the success of the tobacco leaves and potatoes in the banana. Bananas are common in many developing countries and can be stored without refrigeration. "This research opens the door to possibly eradicate many of the diseases that plague third-world countries and harm their children. What child, or adult for that matter, wouldn’t prefer a banana to a needle?" Dr. Thanavala asked.