Eat up your vaccine

Plant extracts provide measles immunity on a plate.
22 July 2002

KENDALL POWELL

Crops could soon boost immunity. © J.Martin

Lettuce might replace booster shots in the next generation of vaccines. Researchers have raised the immunity of mice to measles by feeding them a booster vaccine derived from plants¹.

The study is a step towards an edible measles vaccine for developing countries that would not require refrigeration or skilled medical personnel to deliver jabs. Measles is one of the most contagious human viruses, and kills an estimated 800,000 people a year, predominantly African infants.

"Logistically, if we want to vaccinate 90% of the population in Africa, an oral vaccine is much more sensible," says virologist Steve Wesselingh now at the Macfarlane Burnet Institute for Medical Research and Public Health in Melbourne, Australia.

Wesselingh and his co-workers injected mice with a DNA measles vaccine. It caused the rodents' muscle cells to produce a viral protein on their surface. This primes an animal's immune system to start making antibodies.

21 or 90 days after the first injection the researchers fed the animals tobacco plant juice containing the same viral protein. The extracts came from tobacco plants that had been genetically modified to express the measles protein inside their cells.

These mice had much higher levels of antibodies against measles than animals fed the juice of ordinary plants. Indeed, the combination of DNA and oral vaccine raised antibody levels beyond what is considered protective against measles in humans.

"Not everything that works in mice, works in humans," cautions Gregory Poland, director of the Mayo Vaccine Research Group in Rochester, Minnesota. "But this is good proof-of-principle."

To move towards a truly edible vaccine, the team has expressed the measles protein in lettuce and in rice, which could be ground into cereal for infants. Next they will test their vaccination strategy in macaques or baboons.

Remote access

"An oral vaccine would have profound economic and practical implications if it pans out for human use," says Poland. "It could ease or remove barriers to eradication in the third world."

Traditionally, infants are immunized against measles with injections of a live, weakened form of the measles virus at 1 and 5 years of age.

In developing countries, using a live virus poses several problems. The biggest is keeping the vaccine cold in remote areas that lack electricity. Injecting the vaccine also requires skilled medical personnel and clean needles - both are typically in short supply. The vaccine is also expensive to produce.

DNA vaccine is similarly costly and must be injected, but it is effective at room temperature. So too are edible vaccines derived from plants. These do away with the need for needles and skilled workers and could be produced cheaply in local fields.

Oral test

"The work in measles is an example that perhaps boosting orally can work in a number of situations," says Yasmin Thanavala of the Roswell Park Cancer Institute in Buffalo, New York.

Thanavala's group has developed a potato vaccine booster for use in conjunction with injected hepatitis B vaccine. It is currently in phase I and II clinical trials for patients who have previously been vaccinated².

Edible vaccines could also be useful against diseases that require lifelong boosting. Adults are much more likely to eat food than receive the multiple injections expected for HIV or malaria vaccinations to be effective.

But even if edible vaccines prove effective in humans, getting approval for genetically modified crops and establishing rules for farming and dosing will slow international efforts.

1. Webster, D. E. et al. Successful boosting of a DNA measles immunization with an oral plant-derived measles virus vaccine. Journal of Virology, 76, 7910 - 7912, (2002).
2. Kong, Q. et al. Oral immunization with hepatitis B surface antigen expressed in transgenic plants. Proceedings of the National Academy of Sciences, 98, 11539 - 11544, (2002).