Abstract
The production of vaccines in transgenic plants was first proposed in 1990 however no product has yet reached commercialization. There are several risks during the production and delivery stages of this technology, with potential impact on the environment and on human health. Risks to the environment include gene transfer and exposure to antigens or selectable marker proteins. Risks to human health include oral tolerance, allergenicity, inconsistent dosage, worker exposure and unintended exposure to antigens or selectable marker proteins in the food chain. These risks are controllable through appropriate regulatory measures at all stages of production and distribution of a potential plant-made vaccine. Successful use of this technology is highly dependant on stewardship and active risk management by the developers of this technology, and through quality standards for production, which will be set by regulatory agencies. Regulatory agencies can also negatively affect the future viability of this technology by requiring that all risks must be controlled, or by applying conventional regulations which are overly cumbersome for a plant production and oral delivery system. The value of new or replacement vaccines produced in plant cells and delivered orally must be considered alongside the probability and severity of potential risks in their production and use, and the cost of not deploying this technology – the risk of continuing with the status quo alternative.
Article PDF
Similar content being viewed by others
References
T Arakawa J Yu DK Chong J Hough PC Engen WH Langridge (1998) ArticleTitleA plant-based cholera toxin B subunit-insulin fusion protein protects against the development of autoimmune diabetes Nat Biotechnol 16 934–938 Occurrence Handle10.1038/nbt1098-934 Occurrence Handle9788349
KS Barone DD Tolarova I Ormsby T Doetschman JG Michael (1998) ArticleTitleInduction of oral tolerance in TGF-beta 1 null mice J Immunol 161 154–160 Occurrence Handle9647219
C Carrillo A Wigdorovitz PI Oliveros AM Zamorano AM Sadir GJ Salinas JM Escribano MV Borca (1998) ArticleTitleProtective immune respon to foot-and-mouth disease virus with VP1 expressed in transgenic plants J Virol 72 1688–1690 Occurrence Handle9445079
S Castanon MS Marin JM Martin-Alonso JA Boga R Casais JM Humara RJ Ordas F Parra (1999) ArticleTitleImmunization with potato plants expressing VP60 protein protects against rabbit hemorrhagic disease virus J Virol 73 4452–4455 Occurrence Handle10196345
S Castanon JM Martin-Alonso MS Marin JA Boga P Alonso F Parra R Ordas (2002) ArticleTitleThe effect of the promoter on expression of VP60 gene from rabbit hemorrhagic disease virus in potato plants Plant Sci 162 87–95 Occurrence Handle10.1016/S0168-9452(01)00535-0
Center for Food Safety and Nutrition (1994) FDA BACKGROUNDER: Biotechnology of Food. United States Food and Drug Administration. BG 94-4. May 18, 1994. http://www.cfsan.fda.gov/~lrd/biotechn.html, Last accessed 24 March 2005.
G Conko (2003) ArticleTitleSafety, risk and the precautionary principle: rethinking precautionary approaches to the regulation of transgenic plants Transgenic Res 12 639–647 Occurrence Handle10.1023/B:TRAG.0000005157.45046.8e Occurrence Handle14713193
R Curtiss Suffix3rd (1999) ArticleTitleGenetically modified plants for use as oral immunogens Mucosal Immunology Update 7 10–12
Curtiss R, 3rd and Cardineau GA (1990) Oral immunization by transgenic plants. World Patent Application WO 90/02484. Washington University (Assignee)..
JA DiMasi RW Hansen HG Grabowski (2003) ArticleTitleThe price of innovation: new estimates of drug development costs J Health Econ 22 151–185 Occurrence Handle10.1016/S0167-6296(02)00126-1 Occurrence Handle12606142
K Fujihashi T Dohi MN Kweon JR McGhee T Koga MD Cooper S Tonegawa H Kiyono (1999) ArticleTitlegammadelta T cells regulate mucosally induced tolerance in a dose-dependent fashion Int Immunol 11 1907–1916 Occurrence Handle10590256
S Ghosh P Malhotra PV Lalitha S Guha-Mukherjee VS Chauhan (2002) ArticleTitleExpression of Plasmodium falciparum C-terminal region of merozoite surface protein (PfMSP119), a potential malaria vaccine candidate, in tobacco Plant Sci 162 335–343 Occurrence Handle10.1016/S0168-9452(01)00555-6
I Goklany (2001a) ArticleTitlePrecaution without perversity: a comprehensive application of the precautionary principle to genetically modified crops Biotechnol Law Rep 20 377–396 Occurrence Handle10.1089/073003101750297212
I Goklany (2001b) The Precautionary Principle: A Critical Appraisal of Environmental Risk Assessment Cato Institute Washington, DC
N Gomez A Wigdorovitz S Castanon F Gil R Ordas MV Borca JM Escribano (2000) ArticleTitleOral immunogenicity of the plant derived spike protein from swine-transmissible gastroenteritis coronavirus Arch Virol 145 1725–1732 Occurrence Handle10.1007/s007050070087 Occurrence Handle11003480
TA Haq HS Mason JD Clements CJ Arntzen (1995) ArticleTitleOral immunization with a recombinant bacterial antigen produced in transgenic plants Science 268 714–716 Occurrence Handle7732379
JA Howard KC Donnelly (2004) ArticleTitleA quantitative safety assessment model for transgenic protein products produced in agricultural crops J Agr Environ Ethics 17 545–558 Occurrence Handle10.1007/s10806-004-1470-5
G Jaffe (2004) ArticleTitleRegulating transgenic crops: a comparative analysis of different regulatory processes Transgenic Res 13 5–19 Occurrence Handle10.1023/B:TRAG.0000017198.80801.fb Occurrence Handle15070071
J Kapusta A Modelska M Figlerowicz T Pniewski M Letellier O Lisowa V Yusibov H Koprowski A Plucienniczak AB Legocki (1999) ArticleTitleA plant-derived edible vaccine against hepatitis B virus FASEB J 13 1796–1799 Occurrence Handle10506582
DD Kirk R Rempel J Pinkhasov AM Walmsley (2004) ArticleTitleApplication of Quillaja saponaria extracts as oral adjuvants for plant-made vaccines Expert Opin Biol Ther 4 947–958 Occurrence Handle10.1517/14712598.4.6.947 Occurrence Handle15174976
Kirk DD, Vonhof WM, Eibner J, Mason HS, and Zhang X (2003) Model production of a potent plant-made vaccine. NFID Sixth annual conference on vaccine research, Arlington, VA, May 5–7.
Kirk DD and Webb SR (2005) The next 15 years: taking plant-made vaccines beyond proof of concept. Immunol Cell Biol 83: 248–256.
A Lightman D Sarewitz C Desser (Eds) (2003) Living with the Genie: Essays on Technology and the Quest for Human Mastery Island Press Washington, D.C
L Liu VK Kuchroo HL Weiner (1999) ArticleTitleB7.2 (CD86) but not B7.1 (CD80) costimulation is required for the induction of low dose oral tolerance J Immunol 163 2284–2290 Occurrence Handle10438973
S Ma Y Huang Z Yin R Menassa JE Brandle AM Jevnikar (2004) ArticleTitleInduction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4 Proc Natl Acad Sci USA 101 5680–5685 Occurrence Handle10.1073/pnas.0307420101 Occurrence Handle15056761
SW Ma DL Zhao ZQ Yin R Mukherjee B Singh HY Qin CR Stiller AM Jevnikar (1997) ArticleTitleTransgenic plants expressing autoantigens fed to mice to induce oral immune tolerance Nat Med 3 793–796 Occurrence Handle10.1038/nm0797-793 Occurrence Handle9212110
HS Mason TA Haq JD Clements CJ Arntzen (1998) ArticleTitleEdible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene Vaccine 16 1336–1343 Occurrence Handle10.1016/S0264-410X(98)80020-0 Occurrence Handle9682399
HS Mason DM Lam CJ Arntzen (1992) ArticleTitleExpression of hepatitis B surface antigen in transgenic plants Proc Natl Acad Sci USA 89 11745–11749 Occurrence Handle1465391
Peterson RKD, (2002). How bad times how often: Risk as science. Agbiosafety. University of Nebraska-Lincoln. http://agbiosafety.unl.edu/riskasscience.shtml, Last accessed 24 March 2005.
RKD Peterson CJ Arntzen (2004) ArticleTitleOn risk and plant-based biopharmaceuticals Trends Biotechnol 22 64–66 Occurrence Handle10.1016/j.tibtech.2003.11.007 Occurrence Handle14757039
CS Prakash (1996) ArticleTitleEdible vaccines and antibody producing plants Biotechnol Dev Monit 27 10–13
A Ratliff (2003) ArticleTitleBiotechnology and pharmaceutical R&D and licensing trends: You pays your money and takes your chances J Commercial Biotechnol 10 54–59
Rigano MM, Alvarez ML, Pinkhasov J, Jin Y, Sala F, Arntzen CJ and Walmsley AM (2004) 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 22: 502–508.
Presidential/Congressional Commission on Risk Assessment and Risk Management (1997) Risk Assessment and Risk Management in Regulatory Decision-Making. Final Report, Volume 2.
ES Tackaberry F Prior M Bell M Tocchi S Porter J Mehic PR Ganz R Sardana I Altosaar A Dudani (2003) ArticleTitleIncreased yield of heterologous viral glycoprotein in the seeds of homozygous transgenic tobacco plants cultivated underground Genome 46 521–526 Occurrence Handle10.1139/g03-008 Occurrence Handle12834071
Tacket CO, Clements JD, Wasserman SS and Streatfield SJ (2003) Immunogenicity of a recombinant bacterial antigen delivered in transgenic corn. In NFID sixth annual conference on vaccine research, Arlington, VA, May 5–7.
CO Tacket HS Mason G Losonsky JD Clements MM Levine CJ Arntzen (1998) ArticleTitleImmunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato Nat Med 4 607–609 Occurrence Handle10.1038/nm0598-607 Occurrence Handle9585236
CO Tacket HS Mason G Losonsky MK Estes MM Levine CJ Arntzen (2000) ArticleTitleHuman immune responses to a novel norwalk virus vaccine delivered in transgenic potatoes J Infect Dis 182 302–305 Occurrence Handle10.1086/315653 Occurrence Handle10882612
CO Tacket MF Pasetti R Edelman JA Howard S Streatfield (2004) ArticleTitleImmunogenicity of recombinant LT-B delivered orally to humans in transgenic corn Vaccine 22 4385–4389 Occurrence Handle10.1016/j.vaccine.2004.01.073 Occurrence Handle15474732
Y Thanavala M Mahoney S Pal A Scott L Richter N Natarajan P Goodwin CJ Arntzen HS Mason (2005) ArticleTitleImmunogenicity in humans of an edible vaccine for hepatitis B Proc Natl Acad Sci USA 102 3378–3382 Occurrence Handle10.1073/pnas.0409899102 Occurrence Handle15728371
RM Twyman S Schillberg R Fischer (2005) ArticleTitleTransgenic plants in the biopharmaceutical market Expert Opin Emerg Drugs 10 185–218 Occurrence Handle10.1517/14728214.10.1.185 Occurrence Handle15757412
USDA–APHIS (2004) Transcript of Agriculture Secretary Ann M. Veneman’s remarks regarding Biotechnology Regulations. Washington, D.C. January 22, 2004. http://www. aphis.usda.gov/lpa/issues/biotechcomp/Transcript_of_Biotech _7DB94.doc, Last accessed 24 March 2005.
AM Walmsley ML Alvarez Y Jin DD Kirk SM Lee J Pinkhasov MM Rigano CJ Arntzen HS Mason (2003a) ArticleTitleExpression of the B subunit of Escherichia coli heat-labile enterotoxin as a fusion protein in transgenic tomato Plant Cell Rep 21 1020–1026 Occurrence Handle10.1007/s00299-003-0619-4
Walmsley AM, Rowland L, Kirk DD, Miller TJ and Mason HS (2003b) Efficacy of an edible, plantderived immunocontraceptive vaccine in mice and voles. In NFID Sixth annual conference on vaccine research, Arlington, VA, May 5–7.
J Yu WH Langridge (2001) ArticleTitleA plant-based multicomponent vaccine protects mice from enteric diseases Nat Biotechnol 19 548–552 Occurrence Handle10.1038/89297 Occurrence Handle11385459
V Yusibov DC Hooper SV Spitsin N Fleysh RB Kean T Mikheeva D Deka A Karasev S Cox J Randall H Koprowski (2002) ArticleTitleExpression in plants and immunogenicity of plant virus-based experimental rabies vaccine Vaccine 20 3155–3164 Occurrence Handle10.1016/S0264-410X(02)00260-8 Occurrence Handle12163267
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kirk, D.D., McIntosh, K., Walmsley, A.M. et al. Risk analysis for plant-made vaccines. Transgenic Res 14, 449–462 (2005). https://doi.org/10.1007/s11248-005-5697-3
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11248-005-5697-3