Pharm Crops for Vaccines and Therapeutic Antibodies

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> 31 Aug 2004 17:31:24 -0000

 

> Pharm Crops for Vaccines and Therapeutic

> Antibodies

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> ISIS Press Release 31/08/04

> Pharm Crops for Vaccines and Therapeutic Antibodies

> ******************************************

>

> Prof. Joe Cummins warns of special health impacts of

> vaccine

> and antibodies in pharm crops The extensive

> references to

> this article are posted on ISIS members' website.

> http://www.i-sis.org.uk/full/pbvataFull.php

> Details here.

> http://www.i-sis.org.uk/membership.php

>

> Reckless disregard of known risks The European Union

> (EU)

> recently announced a major program to produce

> plant-based

> vaccines and therapeutic antibodies [1], despite the

> risks

> that came to public attention two years ago [2]. The

> crops

> plants currently used to produce vaccines include

> tobacco,

> maize, potato, tomato, rice and alfalfa. In spite of

> the

> threat to the food supply, maize is a favorite crop

> for

> vaccine production because the transgenic protein

> can be

> concentrated in the kernels. In general, field-test

> releases

> of crop plants modified for vaccine production have

> been

> undertaken with little regard for the health and

> environmental consequences of contaminating food

> crop with

> the vaccine genes.

>

> Risks of vaccine proteins and antibodies Vaccines

> are made

> using antigen proteins from disease organisms such

> as

> viruses or bacteria to elicit production of

> antibodies

> following injection into the blood stream or

> ingestion with

> food. Plant-based vaccines are mainly produced from

> synthetic transgenes whose DNA code words have been

> altered

> for maximal activity in a crop plant [3]. Apart from

>

> vaccines, antibodies are also produced in plants for

>

> treating both animal and plant diseases. These

> antibodies

> are effective, but plagued by the powerful immune

> response

> to the antibodies themselves following repeated

> exposure.

>

> Plant-based vaccines are mainly geared towards

> mucosal

> immunization following oral intake. Oral vaccines

> may elicit

> oral tolerance on repetitive exposure. Oral

> tolerance is the

> animal's defence against antigens in food. Thus,

> after

> repeated exposure to an oral antigen, the mucosal

> immune

> system ceases to view the antigen as such, leaving

> the

> animal susceptible to the pathogen for which the

> vaccine is

> supposed to protect against [4]. The problem of oral

>

> tolerance has been mentioned in at least one review

> of

> plant-based vaccines [5]. Oral tolerance has been

> used to

> treat autoimmune disease such as diabetes by feeding

>

> patients with plants producing an antigen eliciting

> the

> autoimmune response [6]. Oral tolerance to pathogens

> is one

> main threat from the contamination of our food

> supply with

> vaccine genes, whereas therapeutic antibodies

> threaten a

> direct immune response; these two impacts are seldom

>

> discussed by promoters of plant genetic modification

> or by

> science journals reporting the studies.

>

> Risks from synthetic genes and viral vectors Edible

> plant-

> based vaccines have been produced with synthetic

> nuclear

> genes, synthetic chloroplast genes or plant viruses

> modified

> with synthetic genes. These synthetic genes are

> completely

> unknown and untested for toxicities. The nuclear

> transgenes

> frequently failed to produce sufficient protein to

> evoke an

> oral immune response, while chloroplast transgenes

> tended to

> provide adequate protein levels. (Chloroplasts allow

>

> insertion of multiple transgene copies, with less

> problem of

> gene-silencing than nuclear transgene insertions).

> Chloroplast transformations produced antigens at

> high

> levels, up to 25% of total soluble protein while

> nuclear

> inserts generally produced less than 1% total

> soluble

> protein. The endosperm localization of nuclear gene

> products

> can boost antigen levels to 10% of protein in maize

> kernels

> [7]. Numerous plant viruses modified with vaccine

> antigens

> have been released in field tests. Such viruses can

> produce

> vaccine antigen up to10% total soluble protein in

> the

> infected plant but 1% is most frequent [8]. Little

> consideration has been given to containment of these

> GM

> viruses in field tests. They can be spread by

> sucking

> insects, plant wounding or by wind-blown plant

> debris. A

> recent study shows that plant viruses may be spread

> by wind,

> either in water droplets from the plant surface or

> by

> abrasive contact between plant leaves [9]. Box 1

> provides a

> list of 30 human and animal diseases for which

> plant-based

> vaccines have been created. It is worth mentioning

> that

> about half of the transgenic vaccines on the list

> were

> produced using plant viruses as vectors, including

> tobacco

> mosaic virus, cowpea mosaic virus, alfalfa mosaic

> virus,

> potato virus X, plum pox poty virus and tomato bushy

> stunt

> virus. The virus constructions are productive but

> pose

> special long-term risks associated with the release

> of the

> virus to the environment and predictable viral

> recombination

> to produce novel disease agents. Little effort has

> been made

> to monitor these hazardous experiments.

>

>

> Box 1

> Plant-based vaccines [8] Disease agents Species

> protected

> 1. Enterotoxigenic strains of E. coli humans &

> farmed animals

> 2. Vibrio cholerae/ Cholera toxin B subunit

> humans

> 3. Enteropathogenic E. coli/ Pilus structural

> subunit

> A humans

> 4. Vibrio cholerae/ Cholera toxin B subunit,

> rotavirus humans

> 5. Enterotoxigenic strains of E. coli humans

> 6. Hepatitis B virus/ Surface antigen humans

> 7. Hepatitis C virus/ Hypervariable region 1 of

> envelope

> protein 2 fused to cholera toxin humans

> 8. Norwalk virus

> & Rotavirus humans

> 9. Measles/ Haemagglutinin protein humans

> 10. HIV-1/ Peptide of gp41 protein humans

> 11. HIV-1/ V3 loop of gp120 protein humans

> 12. HIV-1/ Peptide of

> transmembrane protein gp41 humans

> 13. HIV-1/ Nucleocapsid protein p24 humans

> 14. Cytomegalovirus/ Glycoprotein B humans

> . Rhinovirus type 14/ Peptide of VP1 protein

> humans

> 16. Respiratory syncytial virus/ Peptides of G

> protein humans

> 17. Staphylococcus aureus/ D2 peptide of

> bronectin-binding protein FnBP humans

> 18. Pseudomonas aeruginosa/ Peptides of

> outer-membrane

> humans

> 19. Protein F Plasmodium falciparum (malaria) &

> Peptides of

> circumsporozoite protein humans

> 20. Human papillomavirus

> type 16/ E7 oncoprotein humans

> 21. Bacillus anthracis/

> Protective antigen humans

> 22. Rabies virus/ Glycoprotein humans, domestic &

> wild animals

> 23. Foot-and-mouth disease virus/ Structural protein

> VP1

> farmed animals

> 24. Transmissible gastroenteritis virus/

> Glycoprotein pigs

> 25. Bovine group A rotavirus/ Major capsid protein

> VP6

> cattle

> 26. Mannheimia haemolytica (bovine pneumonia

> teurellosis)/ Leukotoxin fused to green fluorescent

> protein

> cattle

> 27. Mink enteritis virus/ Peptide of capsid protein

> VP2mink, dogs & cats

> 28. Rabbit haemorrhagic disease virus/ Structural

> protein

> VP60 rabbits

> 29. Rabbit haemorrhagic disease virus rabbits

> 30. Canine arvovirus/ Peptide of capsid protein VP2

> dogs

>

> Numerous plant based therapeutic antibodies for

> treating

> human, animal and plant diseases have been created

> and

> released in field tests. The antibodies are made

> from

> synthetic antibody genes and they are also greatly

> influenced by the pattern of glycosylation (sugar

> modification of protein) produced in the plant [10].

> Further

> examples of plant-based antibodies include mice

> monoclonal

> antibodies that confer resistance to a herbicide by

> binding

> to it, thus inactivating the herbicide [11]. The

> antibody-

> bound herbicide was inactivated but not destroyed,

> and its

> ultimate fate is unknown; presumably it would be

> consumed

> with the transgenic crop. Kholer and Milstein

> discovered a

> method for preparing monoclonal antibodies in 1975

> [12].

> That discovery has made an exceptional contribution

> to the

> development of clinical analytical technology and to

>

> therapy, but that application has not fulfilled the

> expectation of a " magic bullet " for treating disease

> because

> the antibodies provoked a strong immune response if

> applied

> repeatedly.

>

> Risks from cancer and HIV vaccines In the reviews

> mentioned

> previously, numerous plant-based vaccines for

> treating

> infectious diseases have been described [7,8]. I

> shall now

> focus on cancer vaccines and vaccines against human

> immunodeficiency virus (HIV). A vaccine against a

> colorectal

> cancer was produced in tobacco plants [13], as was a

> vaccine

> for treating non-Hodgkins lymphoma [14]. A vaccine

> against

> the papilloma virus oncogene product causing human

> cervical

> cancer was produced using a potato virus-X vector

> carrying

> an antigen of the viral oncogene-encoded protein

> [15]. These

> cancer vaccines are an important effort to control

> cancer,

> but careless environmental release of the vaccines

> in crop

> plants could greatly increase people's

> susceptibility to

> specific cancers through the development of oral

> tolerance.

>

> The Gag gene from Simian Immunodeficiency virus

> (SIV) a

> surrogate for HIV, was used to transform potato

> [16]. In

> that experiment, the native SIV gene was used rather

> than a

> plant enhanced synthetic copy. Failure to alter the

> genetic

> code to the form most active in plants may explain

> the

> relatively low production of Gag protein. In another

>

> experiment, the coat protein of alfalfa mosaic virus

> was

> modified to express antigenic peptides for rabies

> virus and

> HIV. Antibodies against rabies and HIV were

> expressed in

> mice immunized with the antigenic peptides [17].

> Simian-

> human immunodeficiency virus (SHIV) tat gene was

> fused to

> the cholera toxin subunit gene and the combination

> was used

> to transform potato and the fusion protein was found

>

> suitable for mucosal immunization [18]. In none of

> the above

> publications was the potential danger of the

> horizontal

> spread and recombination of the virus genes

> discussed.

>

> A number of technical enhancements have been

> attempted to

> enhance the vaccine antigen production in plants.

> Codon

> usage enhancement has been mentioned [3]. Various

> combinations of promoters and enhancers were used to

> boost

> expression of a gene from rabbit hemorrhagic virus

> in potato

> [19]. The potato patatin promoter proved more

> effective than

> the CaMV or the ubiquitin promoter. Ricin B, a

> lectin sub-

> unit of the deadly poison ricin, has been proposed

> as a

> delivery adjuvant for mucosal vaccines [20]. At

> least as far

> as the published information is concerned,

> plant-based

> vaccines and antibodies are far from ready for major

>

> commercial production. Production of plant-based

> vaccines in

> primary food crops such as maize and rice is

> extremely

> unwise on environmental and health grounds, but a

> recent

> publication indicates that maize, at least, is still

>

> promoted by crop plant vaccine promoters [21].

>

> Regulators must put the brakes on firmly now In

> conclusion,

> there has been extensive creation and field tests of

> plant-

> based vaccines and therapeutic antibodies, with

> little care

> given to the environmental and health consequences

> of the

> field releases. The major accidental exposures of

> the public

> that have come to light have done little to dampen

> the

> accelerating pace of development and testing, most

> of which

> are taking place in secret away from public

> scrutiny. We are

> heading towards a monumental poisoning of our

> primary food

> supply, unless the regulators put the brakes on

> firmly now.

>

>

>

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