Vaccine Cuisine EDIBLE VACCINES. Nina Gloriani Barzaga, M.D.,Ph.D. University of the Philippines Manila

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2 Slide 1 Plant Made Pharmaceuticals EDIBLE VACCINES Vaccine Cuisine Nina Gloriani Barzaga, M.D.,Ph.D. University of the Philippines Manila 3 rd Asian Biotechnology Conference, Manila Nov 9-10, 2006

3 Slide 2 PMPs Plant made pharmaceuticals >> plants as factories produce useful molecules for therapeutic, preventive or diagnostic purposes Molecular farming Biopharming

4 Slide 3 3 Groups of Pharmaceutical proteins produced in plants (PMPs) : 1. Human biopharmaceutical proteins: growth hormone, human serum albumin, β interferon, erythropoietin 2. Recombinant antibodies: IgG1 and IgM 3. Recombinant subunit vaccines (EDIBLE VACCINES): hepatitis B envelope proteins, rabies virus glycoproteins, cholera toxin B subunit

5 Slide 4 Edible Vaccines Edible- means ingested/ eaten/ taken orally In the present day technological concept>> Plant made concept>> Plant made pharmaceuticals or PMPs >> plants as factories produce the vaccine molecules The transgenic plant bearing fruits expressing the vaccine antigen, when eaten, provide the antigenic stimulus that will generate an immune response in the host

6 Slide 5 1. Background & Rationale for Developing Edible Vaccines Advances in the fields of microbiology, molecular biology and immunology provided us with tools for identifying antigenic determinants for a number of infectious agents isolate genes that code for such antigens Salmonella typhi antigens

7 Slide 6 2. Background & Rationale for Developing Edible Vaccines Plant tissue culture methods well developed at this time

8 Slide 7 3. Background & Rationale for Developing Edible Vaccines Advances in plant molecular biology also provided us with techniques to introduce foreign genes into plant species allow the gene products to be expressed and accumulate in certain plant tissues

9 Slide 8 Why Develop Edible Vaccines? Such vaccines are thought to be more cost-effective and reliable in production and delivery, especially for developing countries like the Philippines Do away with injectable vaccines; Edible vaccines are easier, simpler and cheaper to administer; also more acceptable to the public From an immunologic perspective Edible vaccines will elicit mucosal, as well as systemic immunity This will help control transmission at the level where the pathogen enters the host, and also provide systemic immunity X

10 Slide 9 Edible Vaccine Program Clusters UP Manila- UP Los Banos I. Edible Salmonella typhi vaccine II. Edible HIV vaccine III. Edible Rabies vaccine

11 Slide 10 Plant Derived Vaccines under development Rabies Virus Glycoprotein in Transgenic tomatoes G protein coats the outer surface of the rabies virus Plants transformed by Agrobacterium tumefaciens G protein expressed in leaves and tomato fruit Orally administered rabies G protein elicits protective immunity in animals

12 Slide 11 Quality perspectives for Edible vaccines Must meet standards of purity, potency, safety and efficacy defined for vaccines by the World Health Organization The definition of the overall immune response to plant-derived vaccines is of utmost importance Process development- achieving sufficiently high levels of expression of the recombinant antigen in edible plant

13 Slide 12 Future perspectives for Edible vaccines Field and Clinical trials required to define the risk/benefit ratio of a GM plant vaccine Registration Regulation as Pharmaceutical agent Intellectual property right issues Marketing/ Commercialization

14 Slide 13 In what forms are edible vaccines going to be consumed? Initial concept was to feed crude edible plant portion (fruit, leaf or tuber) but it may be difficult to standardise antigen concentration this way Fresh products may have short shelf life Dried products may be more stable, or in dry powder from placed in sachets for mixing with food or drinks These represent more appetising prospects

15 Slide 14 Are edible vaccines for real? Still at an early stage, but experimental know-how and results strongly suggest that plant-derived edible vaccines are likely to be a reality in years Clinical trials with populations at risk are already underway in some laboratories It is generally seen that edible vaccines might overcome some of the difficulties of production, distribution and delivery associated with traditional vaccines

16 Slide 15 PMPs- and the global community UN - Millenium Development Goals 1. Eradicate extreme poverty & hunger 2. Achieve universal primary education 3. Promote gender equality & empower women 4. Reduce child mortality (VACCINES) 5. Improve maternal health 6. Combat HIV/AIDS, malaria and other diseases (VACCINES) 7. Ensure environmental sustainability 8. Develop a global partnership for development ***

17 Slide 16 PMPs UN - Millenium Development Goals: 8. Global partnership Target 17: In cooperation with pharmaceutical companies, provide access to affordable (good quality) essential drugs (and vaccines) in developing countries * Regional cooperation among Asia Pacific Rim developing countries

18 Slide 17 Current BioPharm Companies Planet Biotechnology Dental Caries: CaroRx Colds due to Rhinovirus: RhinoRx Drug-induced Alopecia: DoxoRx Ventria Bioscience Transgenic rice Lactoferrin Lysozyme Prodigene Transgenic corn Trypsin and Aprotinin LEX System Lemna, (duckweed) Rhizosecretion Monoclonal antibodies (Drake et al., 2003) Recombinant proteins (Gaume et al, 2003) Kentucky Tobacco Research and Development Center Trangenic tobacco PMPs and non-protein substances (flavors and fragrances, medicinals, and natural insecticides)

19 Slide 18 Collaborative Project * UP Manila Microbial Immunology Research Group of the College of Public Health Institute of Biotechnology and Molecular Biology -National Institutes of Health ** UP Los Banos Institute of Plant Breeding *** Nagoya City University Graduate School of Medical Sciences ***

20 Slide 19 There s a whole range of possibilities for vaccine cuisine : So, we are looking forward to this vaccine cuisine Bananas con Salmonella, anyone? How about Tomato juice with Vaccine for HIV/AIDS? Let s go for it!!!!