CAMBRIDGE - Axis Genetics plc, of Cambridge, has agreed to an exclusive research and license agreement with the Boyd Thompson Institute (BTI) for Plant Research at Cornell University, which it says will fast track the development and commercialization of edible vaccines made from plants.

BTI, a not-for-profit organization, has pioneered the development of edible vaccines in genetically engineered plants. In May 1998 the institute reported the results of the first human trial of an edible vaccine. Subjects who ate samples of raw potato developed antibodies to the diarrhea-causing subunit E. coli protein, which had been expressed in the potatoes' cells. The trial was published in the May issue of Nature Medicine.

The agreement initially will target two disease areas where no vaccine exists, traveler's diarrhea and Norwalk virus, a water or food-borne infection that causes gastroenteritis. In addition, the two groups will work on an oral vaccine for hepatitis B, where the need for booster doses by injection leads to poor compliance.

Under the agreement, BTI has been granted 15 percent of Axis stock. Axis will fund US$3 million of research at BTI over the next three years, and also will pay $3 million in license fees over this period. In return Axis, which specializes in the production of pharmaceutical proteins in plants, has been granted an exclusive, royalty-free license to develop vaccines based on BTI's technology, material and know-how.

Charles Antzen, president of BTI, said, “This licensing arrangement provides our institute with needed research funding to enable the testing of edible vaccines in clinical trials in the U.S. and U.K. These evaluations will speed acceptance of plant-based vaccines around the world.“

Iain Cubitt, CEO of Axis, said, “This pooling of expertise effectively secures a global lead for two pioneering research organizations which already dominate complimentary areas of expertise with their patented technology and intellectual property.“

Recombinant vaccines produced in plants are designed to elicit a mucosal rather than the conventional systemic immune response. This is expected to make them more effective, because many pathogens enter via the mucosal tissues, which produce 75 percent of the body's immune response. In addition, they will be administered orally, rather than by injection.

Vaccines in plants also would have handling characteristics superior to conventional, injectable vaccines, which often are heat sensitive and must be kept refrigerated. This is a particular problem in developing countries, where there is often no cold chain in place to ensure that vaccines remain effective.

It has been suggested that vaccines could be administered within the whole plant, for example by eating potatoes or bananas that have been genetically engineered to produce the appropriate antigens. But Cubitt does not believe this is practical because of the problem of ensuring that the appropriate dose is administered. He told BioWorld International the plants should be processed to extract the vaccines. The advantage is that this could be done using conventional food processing, rather than expensive pharmaceutical processing techniques.

“Our experience in product development can be applied to the edible vaccines which are now in the prototype stage at the Boyd Thompson Institute,“ said Cubitt. “The recent successful human clinical trial reported by BTI scientists and collaborators, which is the first using biotechnology-derived crops, is predictive of early product introduction for novel oral vaccines against important diseases such as hepatitis and diarrhea.“

Despite this optimism, Cubitt said it would be four to five years before the first product reaches the market.

He outlined the rapid progress being made in developing vaccines from plants Monday at the Biotechnology Industry Organization symposium, in New York. In addition to the potential of BTI's edible plant vaccine technology, Axis's Epicoat technology makes it possible to modify plant viruses so that they become “vaccine factories,“ presenting biologically active polypeptides on their surfaces. Axis has protected mink and dogs against parvovirus infection using virus particles produced in this way.

Rounding out its portfolio of vaccines-from-plants technology, Axis signed a license with Mycogen Corp., of San Diego, in March 1998, giving it the right to develop vaccines for infectious diseases based on Mycogen's plant genetic engineering technology.

Axis Genetics is a privately held company founded in 1993. It has secured three rounds of private funding to date, and expects to complete a fourth later this year. Cubitt said he plans to list the company on the London Stock Exchange next year. *