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Sun-Ripened Vaccines

LONDON--Scientists have for the first time used a vaccine made inside a plant to protect animals--in this case minks--against a viral disease. The achievement, reported in next month's issue of Nature Biotechnology, may herald the start of a new industry for using plants as minifactories to produce vaccines for domestic animals and people.

A four-country team led by Kristian Dalsgaard of the Danish Veterinary Institute for Virus Research in Lindholm, Denmark, engineered the cowpea mosaic virus, which infects plants, to contain a short peptide of 17 amino acids from canine parvovirus. The trick in making this chimera into a good antigen--a foreign body that will stimulate an immune response in the host--is to have the peptide copied many times on the surface of each virus particle. This is no sweat for the cowpea mosaic virus: Its icosahedral surface is composed of 60 copies each of two coat proteins. One has a loop projecting outward that's easily discerned by passing cells. The researchers engineered the viral DNA to include the foreign sequence in this loop, which then gets duplicated 60 times on each virus particle.

Dalsgaard's team injected the engineered virus into the leaves of its natural host, the cowpea plant, also known as the black-eyed bean. After about 3 weeks, the thriving virus population--about 1 to 2 grams of chimeric viral particles per kilogram of plant--was harvested from the juice of minced-up leaves. Because the peptide sequence from the canine parvovirus is also found in two other pathogens, mink enteritis virus and feline panleukopenia virus, the researchers expected that an injection of the chimeric particles would protect the corresponding species--dog, mink, and cat--against the viral diseases. Good vaccines already exist for these diseases, but it could be cheaper to produce other vaccines in plants.

Two groups of mink were vaccinated with the virus particles, six at low dose (100 micrograms) and eight at high dose (1 milligram). About a month later, the animals were exposed to infectious gut contents from an animal with acute mink enteritic viral disease, a debilitating diarrheal illness. Only one mink, in the low-dose vaccine group, became ill. Seven of 10 nonimmunized controls, meanwhile, contracted the disease. The vaccine worked so well that the researchers failed to find even traces of virus in the feces of half the minks immunized. Dalsgaard plans to repeat the experiment in cats.

Experts applaud the study. Says Michael Wilson, deputy director of the Scottish Crop Research Institute in Dundee, U.K., who is developing a similar approach with the potato virus X, "It's very encouraging to see that they've got it to work."