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Plant Based Edible Vaccines
- 1. Plant based E-vaccines Currentstatus and future Bir Bahadur Thapa (24) Central Dept. of Botany, Tribhuwan University, Nepal 2017-04-09 Prepared from reviews based on Dr. Charles Artnzen’s Inventio
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- 3. 400 BC 1796AD 1994 AD Father of MEDICINE Father of IMMUNOLOGY Father of Plant-based Edible Vaccines
- 4. Nepal in 2014 U.S.in 1994 Go out and use Genetic Engineering to create a better virus. 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 5. Inspiratio n can strike anywhere …………!1 35 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 6. What if inaddition to quitting her child, the mother could also administer a lifesaving vaccine in the banana? Chloroplast-less yeast already manufacture expensive Hepatitis B Vaccine in 1980s !! So, why can’t Higher Plant Cells ?? 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 7. What’s wrong withthe traditional ongoing methods? Time 6-9 months/ 10-12 yrs. Cost Upstream expenses Productivity Pandemic diseases 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 8. Why E-vaccines? Needle free CheapStorageSafe 1 35 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24 the developing world's most deadly diseases - cholera, rotavirus, and E. coli infection, to name a few - enter the body through the gastrointestinal tract, a vaccine that is ingested may actually provide the best protection because it mimics the natural route of infection.
- 9. Potato : Advantage Easily transformed. Easilypropagated. Stored for long periods without refrigeration. Disadvantage Need cooking which denature antigen. Tomato Advantage Grow quickly. Cultivate broadly. High content Vitamin-A may boost immune response. Disadvantages Spoils readily. Banana Advantages Do not need cooking. Protein not destroyed even after cooking. Inexpensive . Grown widely in developing countries. Disadvantages Trees take 2-3 years to mature. Spoils rapidly after ripening. Rice Advantages Commonly used in baby food. High expression of antigen. Disadvantages Grows slowly. Requires glasshouse condition. -Well known major crop in 3rd world -Huge biomass for mass production -Not the part of food chain A global killer to a global healer! – Dr. Julian Ma Which Plants? 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 10. Preparation (Edible Vaccines) Directly/ Vector- less (GeneGun) Indirectly/ Via Vector (A. tumefaciens) How to prepare ? 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 11. Action Mechanism Bio- encapsulation (plant cell wall) Peyer’spatches/ Gut Associated Lymphoid Tissue Cells of Immune System T-cells as Infections fighters B-cells as Antibody producers/ IgM Lymphocytes • IgE- allergic reactions • IgG- body fluids • IgA- mucous membranes Macrophage s WBC’s 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 12. Only Systemic Defence BothSystemic & Mucosal/1st line of defence
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- 14. 1 1 1 0 6 Neutralising Antibodies Mucosal Response 1.ETEC (Enterotoxic E. coli 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 15. Immunogenicity of tomatoderived Antigen was much greater than Yeast-derived antigen 30 Tomato plants in guarded greenhouse= 4,000 vaccine do 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 16. 2 0 19/20 Or 95% Seroconversion 1 3 57 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 17. Four doses ofh-EIC (10 μg) codelivered with PIC alone or with PIC and alum Protected 80% of mice against lethal Ebola challenge!! Humanized Ebola immune complexes (h-EICs) Polyinosinic (PIC) as an adjuvent1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
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- 19. Antibody titers was 5times the level protective for human!! 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 20. Dose:- 1 Potato, oncea week for a month Result ?? Better IMMUNED !!! 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 21. The Golden RiceProject wins the patent for Humanity Award 2015 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 22. US $ 250,000/- 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 23. Plants can makemonoclonal antibodies for cancer therapy in sufficient quantities in Soybean as a vehicle for targeting doxorubicin for breast, ovarian, colon and lung tumors. (Prakash 1996) 1 3 5 7 9 1 0 1 3 2 4 6 8 1 1 1 2 1 4 1 7 1 5 1 6 1 8 2 1 1 9 2 0 2 2 2 5 2 3 2 4 Among the autoimmune disorders that might be prevented or eased are type 1 diabetes, rheumatoid arthritis, transplant rejection, etc. (Weiner 1997) Potatoes expressing insulin and ………were able to suppress immune attack in a mouse strain that would become diabetic and could delay the onset of high blood sugar. (Arakawa et. al. 1998) In 2001, a US group tested the first mucosal HIV vaccine in rhesus macaques. While the vaccine showed promising results, it failed to prevent infection. (Belyakov et. Al. 2001)
- 24. So whats theproblem? Who’s against helping sick people? It’s not a pill or in an injection or on a sugar cube. It’s a GMO product and that scares the heck out of people! Others say it can disrupt ecosystem! And what if enters into our food chain……………?? Its ferociously difficult to do ambitious, unproven science!
- 25. Right doses-number andamount Allergic and Toxic substances like nicotine, glycans Scientific challenges 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 26. Regulatory Issues Quality control? Licensing ? Misuse and Overuse 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 27. 1 3 57 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 28. Zambia refused GMmaize in food aid from the United States despite the threat of famine.(http://www.newscientist.com/article.ns?id=dn3073.) Transgenic contamination is unavoidable. Besides pollen, transgenes may spread horizontally by sucking insects, transfer to soil microbes during plant wounding/breakdown of roots/rootlets and may pollute surface and ground water. (http://whyfiles.org/166plant_vaccines/4.html.) Genetic engineering is inherently hazardous because it involves creating vectors/carriers specifically designed to cross wide species barriers, like between plant and animal kingdoms and transferring genes by overcoming their defence mechanisms which are physiologically operative against such genetic assaults. (Ho 1998) The Future of Edible Vaccines 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 29. Emerging multiple herbicide-tolerantvolunteers and weeds (super weeds) and biotech resistant pests demand the use of highly toxic herbicides (atrazine, glufosinate ammonium, glyphosate). (http://www.twnside.org.) Edible vaccines offer major economic and technical benefits in the event of bioterrorism, as their production can be easily scaled up for millions of doses within a limited period of time (smallpox, anthrax, plague, etc.). (http://www.geocities.com/plantvaccines/futureprospects.htm.) The Future of Edible Vaccines 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24 1996 2014 1.7 million Hectares 6 Countries 181.5 million Ha 28 Countries 26 crops approved
- 30. Could we oneday eat plants as a drug instead of processing them? Yes, it’s attractive idea and can be possible, If right doses can be expressed in that plant- With the help of food processing technology!! 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 31. Conclusion 1 3 57 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24 Edible vaccines GMO fear
- 32. Prof. Dr. BijayaPant Dr. Chandra pd. Pokhrel Dr. Sanjaya K. Jha Acknowledge 1 3 5 7 9 10 132 4 6 8 11 12 14 1715 16 18 2119 20 22 2523 24
- 33. Thank you for yourinterest!
- 34. References Arakawa T, YuJ, Chong DK, Hough J, Engen PC, Langridge WH. A plant based cholera toxin B subunit- insulin fusion protein protects against the development of autoimmune diabetes. Nat Biotechnol 1998; 16: 934-8. Belyakov IM, Hel Z, Kelsall B, Kuznetsov VA, Ahlers JD, Nacsa J, Watkins DI, Allen TM, Sette A, Altman J, Woodward R, Markham PD, Clements JD, Franchini G, Strober W, Berzofsky JA. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nat Med. 2001 Dec;7(12):1320-6. de Aizpura HJ, Russell-Jones GJ. Oral vaccination. Identification of classes of proteins that provoke an immune response upon oral feeding. J Exp Med 1988; 167 :440- 51. Haq TA, Mason HS, Clements JD, Arntzen CJ. Oral Immunization with a Recombinant Bacterial antigen produced in transgenic plants. Science 1995; 268 :714-6. Ho MW, Steinbrecher R. Fatal flaws in food safety assessment. Environ Nutr Interact 1998; 2 :51-84. Kapusta J, Modelska A, Figlerowicz M, Pniewski T, Letellier M, Lisowa O, et al . A plant-derived edible vaccine against hepatitis B virus. FASEB J 1999; 13 :1796-9.
- 35. Korban SS, KrasnyanskiSF, Buetow DE. Foods as production and delivery vehicles for human vaccines. J Am Coll Nutr 2002; 21: 212S-7S. Landridge W. Edible vaccines. Scientific Am 2000; 283 :66-71. Mason HS, Haq TA, Clements JD, Arntzen CJ. Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): Potatoes expressing a synthetic LT-B gene. Vaccine 1998; 16 :1336- 43. Mason HS, Lam DM, Arntzen CJ. Expression of hepatitis B surface antigen in transgenic plants. Proc Natl Acad Sci USA 1992; 89 :11745-9. Modelska A, Dietzschold B, Sleysh N, Fu ZF, Steplewski K, Hooper DC, et al . Immunization against rabies with plantderived antigen. Proc Natl Acad Sci USA 1998; 95 :2481-5. Moffat AS. Exploring transgenic plants as a new vaccine source. Science 1995; 268 :658,660. Nemchinov LG, Liang TJ, Rifaat MM, Mazyad HM, Hadidi A, Keith JM. Development of a plant-derived subunit vaccine candidate against hepatitis C virus. Arch Virol 2000; 145 :2557-73. Nugent J, Po AL, Scott EM. Design and delivery of non-parenteral vaccines. J Clin Pharm Ther 1998; 23: 257-85. Prakash CS. Edible vaccines and antibody producing plants. Biotechnol Develop Monitor 1996; 27 :10-3.
- 36. Ramsay AJ, KentSJ, Strugnell RA, Suhrbier A, Thomson SA, Ramshaw IA. Genetic vaccination strategies for enhanced cellular, humoral and mucosal immunity. Immunol Rev 1999; 171: 27-44. Ramshaw IA, Ramsay AJ. The prime-boost strategy: Exciting prospects for improved vaccination. Immunol Today 2000;21 :163-5. Rigano MM, Alvarez ML, Pinkhasov J, Jin Y, Sala F, Arntzen CJ, et al. Production of a fusion protein consisting of the enterotoxigenic Escherichia coli heat-labile toxin B subunit and a tuberculosis antigen in Arabidopsis thaliana . Plant Cell Rep 2004; 22: 502-8. Ruf S, Hermann M, Berger IJ, Carrer H, Bock R. Stable genetic transformation of tomato plastids and expression of a foreign protein in fruit . Nat Biotechnol 2001; 19 :870-5. Tacket CO, Mason HS, Losonsky G, Clements JD, Levine MM, Arntzen CJ. Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato . Nat Med 1998; 4 :607-9. Tacket CO, Mason HS, Losonsky G, Estes MK, Levine MM, Arntzen CJ. Human immune responses to a novel Norwalk virus vaccine delivered in transgenic potatoes. J Infect Dis 2000; 182 :302-5. Tacket CO, Mason HS, Losonsky G, Clements JD, Levine MM, Arntzen CJ. Immunogenicity in humans of a recombinant bacterial-antigen delivered in transgenic potato. Nat Med 1998; 4 :607-9.
- 37. Tacket CO, MasonHS, Losonsky G, Estes MK, Levine MM, Arntzen CJ. Human immune responses to a novel Norwalk virus vaccine delivered in transgenic potatoes. J Infect Dis 2000; 182 :302-5. Webster DE, Cooney ML, Huang Z, Drew DR, Ramshaw IA, Dry IB, et al . Successful boosting of a DNA measles immunization with an oral plant-derived measles virus vaccine. J Virol 2002; 76 :7910-2. Webster DE, Thomas MC, Strugnell RA, Dry IB, Wesselingh SL. Appetising solutions: An edible vaccine for measles. Med J Aust 2002; 176: 434-7. Weiner HL. Oral tolerance for treatment of autoimmune diseases. Ann Rev Med 1997;48:341-51. Wu YZ, Li JT, Mou ZR, Fei L, Ni B, Geng M, et al . Oral immunization with rotavirus VP7 expressed in transgenic potatoes induced high titers of mucosal neutralizing IgA. Virology 2003; 313: 337-42. Yu J, Langridge WH. A plant-based multicomponent vaccine protects mice from enteric diseases . Nat Biotechnol 2001;19 :548-52. "19 Years of Biotech Crops in the World" . isaaa.org. International Service for the Acquisition of Agri-biotech Applications (ISAAA). 2014. Archived from the original(PDF) on 15 Feb 2016. Retrieved 15 February 2016.
Editor's Notes
- #2 This 2 decade old breakthrough lies in forging a link between green plants, foreign DNA, and vaccines. Imagine being able to receive our essential vaccinations by simple eating a banana, potato, lettuce, carrots, and even a tomato. Well, now this is no longer an idea but a reality, all thanks to Dr. Charles Arntzen a scientist that wants to develop a way to end infant mortality in developing countries. Dr. Arntzen developed an oral vaccine that fulfilled the needs of developing countries an inexpensive way to vaccinate their children from infectious diseases. I’ll show what gene(s) were used to create and modified our food to become an edible vaccine, next identify the organism that was the source that provided the gene(s) to make this possible, then explain the purpose of the creating these edible vaccines, and lastly how is this being used today.
- #3 Pharming means farming + pharmaceuticals or manufacturing drugs in plants! The trick with an edible vaccine is convincing a plant to express the genes of a foreign organism.
- #5 This world of medicine has seen its share of its miracle cures from the polio vaccine to heart transplants. So in that respect it’s a simple idea, I cite it as a small step, but a big leap!!
- #6 “Let Food Be Thy Medicine,” a quote attributed to Hippocrates approximately 2,400 years ago. The first history of any vaccine goes back to China, hundreds of years ago, for smallpox. The first experimental use of vaccines goes back 200 years to Jenner in England, where he took a scab of cowpox from a cow and rubbed it on a cut on the arm of a boy, and there was sort of a reaction to it. And then--you never do this today--but he challenged the kid with authentic smallpox. And the boy did not get smallpox, so he made the correlation. And we all remember recent Ebola Outbreak in Africa. From that disease, 2 doctors were been able to survive……….that highlighted every US headlines about those survivors as well as Dr. Charles who has championed the development of edible vaccines in plants, man behind the cure! And became most famous scientist of 2015!!
- #10 While Arntzen's edible vaccine is likely to win approval from children everywhere, there are actually significant medical advantages to this route of administration. An oral vaccine incorporated into a plant bypasses the need for sterile syringes, costly refrigeration, or multiple injections. Furthermore, since many of the developing world's most deadly diseases - cholera, rotavirus, and E. coli infection, to name a few - enter the body through the gastrointestinal tract, a vaccine that is ingested may actually provide the best protection because it mimics the natural route of infection. WHO estimates that nearly 3-10 millions of children around the world each year are dying from vaccine preventable diseases like measles, Hepatitis and even Diarrhea!
- #11 1in every 5 American deaths is due to this tobacco, one of the most lethal killers in 21st century!
- #12 Nowadays plants are no longer genetically modified but simply infiltrated or submerged in a solution with a modified plant virus that reprograms them to make the desired pharmaceutical protein. They use bacterium Agrobacterium tumefaciens since it will deliver the necessary genetic blueprints so the plant can successfully become an edible vaccine. But before that, u should remove genes coding cytokinins and auxins those are responsible for crown gall. Once infiltrated, leaves begin producing drugs in just hours. Within days, they are harvested, ground up and filtered, and the medicine is purified.
- #15 The goal of current mucosal vaccination strategies is to prevent both initial stages of disease (colonization and infection by pathogens) and block its development. Mucosal vaccines have several advantages over traditional systemic vaccines. They can be administered orally or nasally rather than via injection. This is more widely accepted by the public, as well as making the vaccine simpler to administer and distribute. In addition, there is less risk of needle stick injury or cross-contamination
- #19 Hepatitis B persists as a common human disease despite effective vaccines having been employed for almost 30 years.
- #21 VLP is a hollow virus particle without any genes coding for virulence. It cannot replicate either. But it mimics the original virus in shape which agitates our body, thus activating active and fast antibodies against that antigen with longer "immunological memory" of infectious pathogens to facilitate early detection and to confer protective immunity against a rechallenge. Because non-replicating subunit vaccines offer the possibility of formulation for cost-effective, long-term storage in bio-threat reduction repositories, EIC is an attractive option for public health defence measures. Co-delivery of the Ebola immune complexes with Toll-like receptor agonists elicited a more robust antibody response in mice than did EIC alone.
- #22 The only FDA approved plant made drug ELEYSO, against inflammations is available in carrot cells.
- #25 the Nobel Prize for Food and Agriculture equivalent that in 2016 marks the 30th anniversary of the establishment of the World Food Prize by the late Nobel Peace Prize Laureate Dr. Norman E. Borlaug.
- #27 Because 70-80% of people contract the disease mucosally, and because the gut is the major reservoir for HIV replication, there is interest in the potential of the mucosal immune response in preventing and/or clearing infection.
- #29 To determine the right dosage, one needs to consider the person's weight, age; fruit/plant's size, ripeness and protein content. The amount to be eaten is critical, especially in infants, who might spit it, eat a part or eat it all and throw it up later. Too low a dose would fail to induce antibodies and too high a dose would, instead, cause tolerance. Concentrating the vaccine into a teaspoon of baby food may be more practical than administering it in a whole fruit.
- #30 It is still unclear whether the edible vaccines would be regulated under food, drugs or agricultural products and what vaccine component would be licensed - antigen itself, genetically engineered fruit or transgenic seeds. Although edible vaccines fall under "GM" plants, it is hoped that these vaccines will avoid serious controversy, because they are intended to save lives.
- #34 But it’s a long drive, ultimately Dr. Charles inspiration will come true. He had already made the first step……. We will do the rest!
- #35 Edible plant-derived vaccine may lead to a future of safer and more effective immunization. They would overcome some of the difficulties associated with traditional vaccines, like production, distribution and delivery and they can be incorporated into the immunisation plans. They have passed the major hurdles in the path of an emerging vaccine technology. Before becoming a reality, the technical obstacles, though all seem surmountable, need to be overcome. However, with limited access to essential health care in much of the world and with the scientific community still struggling with complex diseases like HIV, malaria, etc, a cost-effective, safe and efficacious delivery system in the form of edible vaccines will become an essential component in our disease-prevention arsenal.