30 July 2002 14:30 EST

by Joanne Clough, Drug Discovery Today

Another team of researchers from New York State have turned to the potato as a vaccine vehicle. Sent forth barely a year ago as an edible way to prevent hepatitis B by a team at Cornell University, the humble spud is now being engineered as a vegetable vaccine against papilloma virus.

Mice will develop an immune response against human papilloma virus (HPV), the cause of cervical cancer, if they eat potatoes containing a vaccine directed against it. The research team has engineered the potato vaccine for those to whom it matters urgently - women in developing countries, where 80% of deaths from cervical cancer occur.

'The beauty of an oral vaccine is that you don't need a needle," said Robert Rose, assistant professor of medicine, microbiology, and immunology at the University of Rochester Medical Center. "In most cases you don't even need a doctor."

Human papilloma virus is one of the most common sexually transmitted diseases, and the cause of virtually all cases of cervical cancer. Not all types of HPV cause pre-cancerous changes, but certain strains of the virus incorporate themselves into cell nuclei and cause the cell to divide abnormally. Screening can detect cervical cancer, and vaccines are in development. But at present preventive measures such as safe sex and limiting the numbers of sexual partners are the only sure ways to avoid infection.

The prospect of delivering vaccines by transgenic fruits or vegetables in developing countries is a "very attractive" way to prevent cancer in large numbers of women at low cost, said Martin Bachmann, Executive Vice President and Chief Scientific Officer at Cytos Biotechnology, because powerful diagnostic tools are largely missing in these areas.

Introducing novel vaccines to developing countries is a major problem, he observed, largely because of the cost and distribution problems. "Since raw potatoes may not be particularly delicious to eat, it remains to be seen whether this particular choice of vegetable turns out to be optimal," he added. "On the other hand, who would not want to prevent his sexual diseases with a beer and chips?"

The researchers in Rochester began studying HPV in the 1980s, but the latest developments are a collaboration between scientists at Rochester and others at Cornell University and Tulane University Health Sciences Center.

In the early 1990s, the Rochester team isolated the gene sequence of the HPV protein envelope, and created virus-like particles (VLPs) which are non-infectious but resemble viral particles. Immunization with VLPs, they found, could induce potentially protective immunity against infection. Oral vaccinations in mice induced serum IgA and IgG antibodies against VLP that efficiently neutralized HPV (type 11) virions in vitro.

In 1997, the group began a VLP vaccination study in human volunteers. The subjects tolerated the vaccine well, they found, and it induced high levels of binding and neutralizing antibodies. The VLP technology using an injectable form of the vaccine against HPV is currently in Phase II trials; Rose expects that Phase III trials will soon follow at GlaxoSmithKline.

However, of the 230,000 or so women who die of cervical cancer every year, about 80% of them in developing countries, where annual checkups are almost non-existent and injections are expensive and difficult to deliver. Enter the potato, into which the team inserted VLP-encoding DNA; they later found VLP expressed in the leaves and potatoes themselves.

In preclinical studies, they fed mice the transgenic potato, containing 5 microgram doses of VLP, each week for four weeks, followed by a booster after a further two weeks with an otherwise sub-immunogenic oral dose of purified VLPs. Those mice that ate HPV transgenic potatoes in combination with adjuvant had increased levels of antibodies against HPV.

Recent results also show that VLPs are immunogenic when co-administered with transdermal patches containing of Escherichia coli LT(R192G), a heat-labile enterotoxin (developed by John Clements at Tulane) which contains a mutation that prevents activation and toxicity, producing a non-specific adjuvant. These mice had higher titers of serum antibody to VLP than animals immunized with VLPs alone.

Potatoes are only one edible, and perhaps not the best choice, among a whole cornucopia being considered as vehicles for vaccines: Other researchers have garnished bananas, tomatoes, apples, soybeans, corn, and other edibles with vaccine.

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