Plant-based_vaccines_face_big_scientific_and_regulatory_hurdles

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Plant-based_vaccines_face_big_scientific_and_regulatory_hurdles

 

> " GM_WATCH " <info

> Sun, 5 Sep 2004 23:14:40 +0100

 

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> http://www.gmwatch.org

> ---

> " Instead of being immunized, patients could even end

> up being 'tolerized,' meaning an immune response

> against future invaders would be weakened, not

> intensified. "

>

> For a GM WATCH profile of Charles Arntzen see:

> http://www.gmwatch.org/profile1.asp?PrId=13 & page=A

> ---

> Nature Medicine 10, 881 (2004)

> doi:10.1038/nm0904-881

>

> News

>

> Edible vaccines not ready for main course

> Peter Vermij

> Amsterdam

>

> Plant-based vaccines face big scientific and

> regulatory hurdles

>

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v10/n9/full/nm0904-8\

81.html

>

> [image caption - Food for thought: Plant-based

> vaccines not yet ripe enough for harvesting.]

>

> Edible vaccines produced in genetically modified

> crops promise cheap and effective protection against

> infectious diseases in the developing world. But

> vaccine manufacturers are reluctant to take a bite

> out of the projects.

>

> Since 1992, when biologist Charles Arntzen proposed

> genetically modifying bananas to serve as cheap

> vaccines against infectious diseases, research on

> plant-based pharmaceuticals has grown rapidly. In

> July, the European Union promised 12 million to

> European and South African scientists developing

> vaccines or antibodies against HIV/AIDS, rabies and

> tuberculosis. Work is further ahead in the US, where

> several acres of crops, most of them still

> experimental, are planted each year.

>

> Researchers have thus far produced more than 45

> different antigens in a wide range of plants. " In

> 10–15 years, " says Hilary Koprowski, a veteran

> vaccine researcher at Thomas Jefferson University,

> " plant-derived vaccines will be fully appreciated. "

>

> At least in theory, plant-based vaccines would be

> safer than those produced in animal tissues because

> the chances of unknown human pathogens hitching a

> ride would be extremely small. Costs per dose would

> be low, and scaling up would just mean planting a

> larger crop. During transport and storage,

> vaccine-containing seeds or dried leaves would not

> need refrigeration, a significant advantage in

> developing countries. Oral vaccines especially,

> administered as juices or tablets to circumvent dose

> variability, would pave the way for mass

> vaccinations in those countries.

>

> But even Arntzen now says his original idea of

> distributing vaccine-bearing fruit was naive,

> because regulatory agencies will not approve

> vaccines with variable dosing.

>

> Many in the field say that, at least in animals,

> plant-based oral vaccines have been proven to be

> safe and effective. For instance, corn loaded with

> proteins from a gastroenteritis virus is effective,

> at least when used as a booster, in protecting pigs

> against the disease, says John Howard, founder of

> the Texas-based firm ProdiGene.

>

> In humans, several vaccines have passed safety

> trials. Arntzen's group at Arizona State University

> tried vaccines produced in genetically modified

> potatoes and corn against enterotoxic Escherichia

> coli and Norwalk virus. Koprowski's group fed

> volunteers spinach containing a rabies booster

> vaccine. Both groups have tested oral hepatitis B

> vaccines, either as primary or booster vaccine, in

> lettuce, spinach and potatoes.

>

> Although small phase 1 trials like these can't prove

> protection, volunteers in the studies showed an

> " appropriate, " though not always strong, immune

> response, Arntzen says.

>

> Arntzen is collaborating with companies in Egypt,

> South Africa and South Korea, but outside developing

> nations, where there is an urgent need for such

> vaccines, finding manufacturers willing to finance

> larger trials to demonstrate efficacy has been a

> formidable challenge. " I've talked to all of the

> [big companies], " says Koprowski, " and so far I

> regard it a waste of time. "

>

> Vaccine manufacturers have little reason to replace

> existing production lines, as most vaccines are

> economically unattractive. The medical community is

> also focused on high-tech approaches, making

> farm-grown vaccines a tough sell, Koprowski says.

> But smaller companies, led by young people willing

> to take risks, could challenge the current thinking,

> he says. " Then, others will follow. "

>

> Part of the hesitation stems from the fact that

> plant-based oral vaccines constitute a new

> technology from both a regulatory and scientific

> perspective, says renowned vaccinologist Stanley

> Plotkin, who now advises Aventis Pasteur.

>

> Before they can be approved, Plotkin says,

> plant-based vaccines will have to consistently

> generate stronger immune responses, which would need

> to be studied carefully for every crop. " If vaccines

> are intimately presented together with food, the

> gut's immune system faces a conundrum, " he notes.

> The gut is designed not to react to antigens in

> food, but must produce a useful response against the

> vaccine. Instead of being immunized, patients could

> even end up being 'tolerized,' meaning an immune

> response against future invaders would be weakened,

> not intensified.

>

> Researchers say they have not yet seen signs of such

> tolerance, but Plotkin says experiments to convince

> regulators have yet to be designed. " Immunologists

> will have to figure out how the gut can do this, and

> do it right 99.9999% of the time, " he says.

> Producing veterinary vaccines first, followed by

> human booster vaccines, could be the sensible way

> forward, he adds.

>

> Convincing the general public that it is safe to

> grow vaccines in fields poses a bigger challenge.

> Citing fears over supermarket shelves stocked with

> vaccine-contaminated foods, consumer groups have

> called for a ban on using food crops to produce

> pharmaceuticals. Some companies are avoiding the

> issue by developing injectable plant-based vaccines,

> by using nonfood crops or by not using genetically

> modified crops.

>

> For instance, California-based Large Scale Biology

> uses genetically engineered mosaic viruses to infect

> tobacco plants. A few weeks later, says Larry Grill,

> the company's chief scientific officer, antibodies

> can be purified from the harvested leaves. The

> company has produced patient-specific antibodies

> against cancer cells just months after biopsies were

> taken.

>

> Once the scientific and regulatory hurdles are

> cleared, convincing skeptics will be easier,

> researchers note. " If I could save millions of lives

> in developing countries, " says Arntzen, " I think I'd

> have a pressure group that could stand up even

> against Greenpeace in Europe. "

>