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Expert Opinion on Biological Therapy Volume 19, 2019 - Issue 6
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Review

An overview of tolerogenic immunotherapies based on plant-made antigens

Dania O. Govea-AlonsoLaboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México;Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, MéxicoView further author information
,
Jaime I. Arevalo-VillalobosLaboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México;Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, MéxicoView further author information
,
Verónica A. Márquez-EscobarLaboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México;Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, MéxicoView further author information
,
Sornkanok VimolmangkangDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand;Research Unit for Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok, ThailandView further author information
&
Sergio Rosales-MendozaLaboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México;Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, MéxicoCorrespondence[email protected]
View further author information
Pages 587-599 | Received 15 Dec 2018, Accepted 16 Mar 2019, Published online: 22 Apr 2019

  • Kesik-Brodacka M. Progress in biopharmaceutical development. Biotechnol Appl Biochem. 2018;65(3):306–322.
  • Hefferon K. Plant-derived pharmaceuticals for the developing world. Biotechnol J. 2013;8(10):1193–1202.
  • Govea-Alonso DO, Cardineau GA. Principles of plant-based vaccines. In: Rosales-Mendoza S, editor. Genetically engineered plants as a source of vaccines against wide spread diseases, an integrated view. New York (NY): Springer; 2014. p. 1–14.
  • Curtiss RIII, Cardineau GA Oral immunization by transgenic plants. 1997 United States Patent 5,654,184.
  • Gleba Y, Marillonnet S, Klimyuk V. Engineering viral expression vectors for plants: the ‘full virus’ and the ‘deconstructed virus’ strategies. Curr Opin Plant Biol. 2004;7:182–188.
  • Oey M, Lohse M, Kreikemeyer B, et al. Exhaustion of the chloroplast protein synthesis capacity by massive expression of a highly stable protein antibiotic. Plant J. 2 009;57:436–445.
  • Su J, Zhu L, Sherman A, et al. Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B. Biomaterials. 2015;70:84–93.
  • Pillet S, Aubin É, Trépanier S, et al. A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults. Clin Immunol. 2016;168:72–87.
  • Lomonossoff GP, D’Aoust MA. Plant-produced biopharmaceuticals: a case of technical developments driving clinical deployment. Science. 2016;353(6305):1237–1240.
  • Landry N, Ward BJ, Trépanier S, et al. Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. PLoS One. 2010;5(12):e15559.
  • Tekoah Y, Shulman A, Kizhner T, et al. Large-scale production of pharmaceutical proteins in plant cell culture-the Protalix experience. Plant Biotechnol J. 2015;13(8):1199–1208.
  • PREVAIL II Writing Group; Multi-National PREVAIL II Study Team, Davey RT Jr, Dodd L, Proschan MA, et al. Controlled trial of zmapp for ebola virus infection. N Engl J Med. 2016;375(15):1448–1456.
  • Wambre E, Jeong D. Oral tolerance development and maintenance. Immunol Allergy Clin North Am. 2018;38(1):27–37.
  • Hamad A, Burks W. Oral tolerance and allergy. Semin Immunol. 2017;30:28–35.
  • Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol. 2003;3(4):331–341.
  • Jutel M, Kosowska A, Smolinska S. Allergen immunotherapy: past, present, and future. Allergy Asthma Immunol Res. 2016;8(3):191–197.
  • McDole JR, Wheeler LW, McDonald KG, et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature. 2012;483(7389):345–349.
  • Berin MC, Shreffler WG. Mechanisms underlying induction of tolerance to foods. Immunol Allergy Clin North Am. 2016;36(1):87–102.
  • Schiavi E, Smolinska S, O’Mahony L. Intestinal dendritic cells. Curr Opin Gastroenterol. 2015;31(2):98–103.
  • Aliberti J. Immunity and tolerance induced by intestinal mucosal dendritic cells. Mediators Inflamm. 2016;2016:3104727.
  • Mann ER, Landy JD, Bernardo D, et al. Intestinal dendritic cells: their role in intestinal inflammation, manipulation by the gut microbiota and differences between mice and men. Immunol Lett. 2013;150:30–40.
  • Hadis U, Wahl B, Schulz O, et al. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity. 2011;34(2):237–246.
  • Sakaguchi S, Wing K, Miyara M. Regulatory T cells - a brief history and perspective. Eur J Immunol. 2007;37:S116–23.
  • Dominguez-Villar M1, Hafler DA2. Regulatory T cells in autoimmune disease. Nat Immunol. 2018;19(7): 665–673. 3
  • Singer BD, King LS, D’Alessio FR. Regulatory T cells as immunotherapy. Front Immunol. 2014;5:46.
  • Zhao H, Liao X, Kang Y. Tregs: where we are and what comes next? Front Immunol. 2017;8:1578.
  • American Academy of Allergy, Asthma & Immunology [Internet]. Descriptive note for allergies. Milwaukee, WI: AAAAI; 2017. 2018 Oct 04. cited ]., Available from: http://www.aaaai.org/conditions-and-treatments/allergies .
  • Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol. 2014;134(5):1016–25.e43.
  • Rael E. Allergen immunotherapy. Prim Care. 2016;43(3):487–494.
  • Takaiwa F, Yang L. Development of a rice-based peptide vaccine for Japanese cedar and cypress pollen allergies. Transgenic Res. 2014;23(4):573–584.
  • Frew AJ. Allergen immunotherapy. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S306–13.
  • Larche M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6:761–771.
  • Ma S, Liao YC, Jevnikar AM. Induction of oral tolerance with transgenic plants expressing antigens for prevention/treatment of autoimmune, allergic and inflammatory diseases. Curr Pharm Biotechnol. 2015;16(11):1002–1011.
  • Krebitz M, Wiedermann U, Essl D, et al. Rapid production of the major birch pollen allergen Bet v 1 in Nicotiana benthamiana plants and its immunological in vitro and in vivo characterization. FASEB J. 2000;14(10):1279–1288.
  • Okada A, Okada T, Ide T, et al. Accumulation of Japanese cedar pollen allergen, Cry j 1, in the protein body I of transgenic rice seeds using the promoter and signal sequence of glutelin GluB-1 gene. Mol Breed. 2003;12:61–70.
  • Takagi H, Saito S, Yang L, et al. Oral immunotherapy against a pollen allergy using a seed-based peptide vaccine. Plant Biotechnol J. 2005;3:521–533.
  • Takagi H, Hiroi T, Yang L, et al. A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. Proc Natl Acad Sci USA. 2005;102:17525–17530.
  • Takagi H, Hirose S, Yasuda H, et al. Biochemical safety evaluation of transgenic rice seeds expressing T cell epitopes of Japanese cedar pollen allergens. J Agric Food Chem. 2006;54:9901–9905.
  • Takaiwa F, Hirose S, Takagi H, et al. Deposition of a recombinant peptide in ER-derived protein bodies by retention with cysteine-rich prolamins in transgenic rice seed. Planta. 2009;229:1147–1158.
  • Takagi H, Hiroi T, Hirose S, et al. Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides. Peptides. 2010;31:1421–1425.
  • Lee CC, Ho H, Lee KT, et al. Construction of a Der p2-transgenic plant for the alleviation of airway inflammation. Cell Mol Immunol. 2011;8:404–414.
  • Suzuki K, Kaminuma O, Yang L, et al. Prevention of allergic asthma by vaccination with transgenic rice seed expressing mite allergen: induction of allergen-specific oral tolerance without bystander suppression. Plant Biotechnol J. 2011;9(9):982–990.
  • World Health Organization [Internet]. Geneva, Switzerland: WHO; 2017 Asthma fact sheet N° 307. [ cited 2018 Oct 14]. Available from: http://www.who.int/mediacentre/factsheets/fs307/en/
  • Bisgaard H, Szefler S. Prevalence of asthma-like symptoms in young children. Pediatr Pulmonol. 2007;42(8):723–728.
  • Yukselen A, Kendirli SG. Role of immunotherapy in the treatment of allergic asthma. World J Clin Cases. 2014;2(12):859–865.
  • Deo SS, Mistry KJ, Kakade AM, et al. Role played by Th2 type cytokines in IgE mediated allergy and asthma. Lung India. 2010;27(2):66–71.
  • Mishan-Eisenberg G, Borovsky Z, Weber MC, et al. Differential regulation of Th1/Th2 cytokine responses by placental protein 14. J Immunol. 2004;173(9):5524–5530.
  • Ngoc PL, Gold DR, Tzianabos AO, et al. Cytokines, allergy, and asthma. Curr Opin Allergy Clin Immunol. 2005;5(2):161–166.
  • Smart V, Foster PS, Rothenberg ME, et al. A plant-based allergy vaccine suppresses experimental asthma via an IFN-gamma and CD4+CD45RBlow T cell-dependent mechanism. J Immunol. 2003;171(4):2116–2126.
  • Suzuki K, Kaminuma O, Yang L, et al. Prevention of allergic asthma by vaccination with transgenic rice seed expressing mite allergen: induction of allergen-specific oral tolerance without bystander suppression. Plant Biotechnol J. 2011;9(9):982–989.
  • Li C, Jiang Y, Guo W, et al. Production of a chimeric allergen derived from the major allergen group 1 of house dust mite species in Nicotiana benthamiana. Hum Immunol. 2013;74(5):531–537.
  • Tuomilehto J. The emerging global epidemic of type 1 diabetes. Curr Diab Rep. 2013;13(6):795–804.
  • Maahs DM, West NA, Lawrence JM, et al. Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am. 2010;39:481–497.
  • D’Angeli MA, Merzon E, Valbuena LF, et al. Environmental factors associated with childhood-onset type 1 diabetes mellitus: an exploration of the hygiene and overload hypotheses. Arch Pediatr Adolesc Med. 2010;164:732–738.
  • Wilkin TJ. The accelerator hypothesis: a review of the evidence for insulin resistance as the basis for type I as well as type II diabetes. Int J Obes. 2009;33:716–726.
  • Ferrannini E, Mari A, Nofrate V, et al. Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset. Diabetes. 2010;59:679–685.
  • Gianani R, Eisenbarth GS. The stages of type 1A diabetes: 2005. Immunol Rev. 2005;204:232–249.
  • Lee AS, Ghoreishi M, Cheng WK, et al. Toll-like receptor 7 stimulation promotes autoimmune diabetes in the NOD mouse. Diabetologia. 2011;54(6):1407–1416.
  • Lang KS, Recher M, Junt T, et al. Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease. Nat Med. 2005;11(2):138–145.
  • Zhang Y, Lee AS, Shameli A, et al. TLR9 blockade inhibits activation of diabetogenic CD8+ T cells and delays autoimmune diabetes. J Immunol. 2010;184(10):5645–5653.
  • Hu C, Ding H, Li Y, et al. NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets. Proc Natl Acad Sci USA. 2015;112(36):11318–11323.
  • Wen L, Ley RE, Volchkov PY, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature. 2008;455(7216):1109–1113.
  • Uno S, Imagawa A, Okita K, et al. Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumour necrosis factor-alpha in patients with recent-onset type 1 diabetes. Diabetologia. 2007;50(3):596–601.
  • Tai N, Wong FS, Wen L. The role of the innate immune system in destruction of pancreatic beta cells in NOD mice and humans with type I diabetes. J Autoimmun. 2016;71:26–34.
  • Control TD, Group CTR, Nathan DM, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977–986.
  • Arakawa T, Yu J, Chong DK, et al. A plant based-cholera toxin B subunit insulin fusion protein protects against the development of autoimmune diabetes. Nat Biotechnol. 2016;16(10):934–938.
  • Porceddu A, Falorni A, Ferradini N, et al. Transgenic plants expressing human glutamic acid decarboxylase(GAD65), a major autoantigen in insulin-dependent diabetes mellitus. Mol Breed. 1999;5(6):553–560.
  • Avesani L, Falorni A, Tornielli GB, et al. Improved in planta expression of the human islet autoantigen glutamic acid decarboxylase (GAD65). Transgenic Res. 2003;12(2):203–212.
  • Avesani L, Vitale A, Pedrazzini E, et al. Recombinant human GAD65 accumulates to high levels in transgenic tobacco plants when expressed as an enzymatically inactive mutant. Plant Biotechnol J. 2010;8(8):862–872.
  • Li D, O’Leary J, Huang Y, et al. Expression of cholera toxin B subunit and the B chain of human insulin as a fusion protein in transgenic tobacco plants. Plant Cell Rep. 2006;25(5):417–424.
  • Ma S, Huang Y, Yin Z, et al. Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. Proc Natl Acad Sci USA. 2004;101(15):5680–5685.
  • Merlin M, Gecchele E, Arcalis E, et al. Enhanced GAD65 production in plants using the MagnICON transient expression system: optimization of upstream production and downstream processing. Biotechnol J. 2016;11(4):542–553.
  • Smolen JS, Aletaha D, Redlich K. The pathogenesis of rheumatoid arthritis: new insights from old clinical data? Nat Rev Rheumatol. 2012;8(4):235–243.
  • Arend WP, Firestein GS. Pre-rheumatoid arthritis: predisposition and transition to clinical synovitis. Nat Rev Rheumatol. 2012;8(10):573–586.
  • Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003;423(6937):356–361.
  • McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328–2337.
  • Ohnishi Y, Tsutsumi A, Matsumoto I, et al. Altered peptide ligands control type II collagen-reactive T cells from rheumatoid arthritis patients. Mod Rheumatol. 2006;16(4):226–228.
  • Lizuka M, Wakasa Y, Tsuboi H, et al. Suppression of collagen-induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of type II collagen. Plant Biotechnol J. 2014;12(8):1143–1152.
  • Lizuka M, Wakasa Y, Tsuboi H, et al. Prophylactic effect of the oral administration of transgenic rice seeds containing altered peptide ligands of type II collagen on rheumatoid arthritis. Biosci Biotechnol Biochem. 2014;78(10):1662–1668.
  • Hansson C, Schön K, Kalbina I, et al. Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis. Plant Biotechnol J. 2016;14(4):1106–1115.
  • Hirota T, Tsuboi H, Iizuka-Koga M, et al. Suppression of glucose-6-phosphate-isomerase induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of glucose-6-phosphate-isomerase. Mod Rheumatol. 2017;27(3):457–465.
  • Mannucci PM, Tuddenham EG. The hemophilias–from royal genes to gene therapy. N Engl J Med. 2001;344(23):1773–1779.
  • Bolton-Maggs PH, Pasi KJ. Haemophilias A and B. Lancet. 2003;361(9371):1801–1809.
  • Mannucci PM, Franchini M. Is haemophilia B less severe than haemophilia A? Haemophilia. 2013;19(4):499–502.
  • Terada K, Yagi Y, Niizuma T, et al. Is oral tolerance therapy possible for haemophilia with inhibitors? Vox Sang. 2001;80(1):61–62.
  • Verma D, Moghimi B, LoDuca PA, et al. Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice. Proc Natl Acad Sci USA. 2010;107(15):7101–7106.
  • Wang X, Su J, Sherman A, et al. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells. Blood. 2015;125(15):2418–2427.
  • Su J, Zhu L, Sherman A, et al. Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B. Biomaterials. 2015;70:84–93.
  • Herzog RW, Nichols TC, Su J, et al. Oral tolerance induction in hemophilia B dogs fed with transplastomic lettuce. Mol Ther. 2017;25(2):512–522.
  • Sherman A, Su J, Lin S, et al. Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells. Blood. 2014;124(10):1659–1668.
  • Chan AC1, Pj C. Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol. 2010;10(5):301–316.
  • Galeotti C, Kaveri SV, Bayry J1. IVIG-mediated effector functions in autoimmune and inflammatory diseases. Int Immunol. 2017;29(11):491–498.
  • Abbas AK, Trotta E, Simeonov D R, et al. Revisiting IL-2: biology and therapeutic prospects. Sci Immunol. 2018;3(25):eaat1482.
  • Bacher P, Scheffold A. The effect of regulatory T cells on tolerance to airborne allergens and allergen immunotherapy. J Allergy Clin Immunol. 2018;142(6):1697–1709.
  • Pozsgay J, Szekanecz Z, Sármay G. Antigen-specific immunotherapies in rheumatic diseases. Nat Rev Rheumatol. 2017;13(9):525–537.
  • Wraith DC. The future of immunotherapy: a 20 year perspective. Front Immunol. 2017;8:1668.
  • Ruhlman T, Ahangari R, Devine A, et al. Expression of cholera toxin B-proinsulin fusion protein in lettuce and tobacco chloroplasts: oral administration protects against development of insulitis in non-obese diabetic mice. Plant Biotechnol J. 2016;5:495–510.
  • Boyhan D, Daniell H. Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide. Plant Biotechnol J. 2011;9(5):585–598.
  • Lakshmi PS, Verma D, Yang X. Low cost tuberculosis vaccine antigens in capsules: expression in chloroplasts, bio-encapsulation, stability and functional evaluation in vitro. PLoS One. 2013;8(1):e54708.
  • Kwon KC, Daniell H. Low-cost oral delivery of protein drugs bioencapsulated in plant cells. Plant Biotechnol J. 2015;13(8):1017–1022.
  • Peyret H, Lomonossoff GP. When plant virology met Agrobacterium: the rise of the deconstructed clones. Plant Biotechnol J. 2015;13(8):1121–1135.
  • Bendandi M, Marillonnet S, Kandzia R, et al. Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin’s lymphoma. Ann Oncol. 2010;21(12):2420–2427.
  • Klimyuk V, Pogue G, Herz S, et al. Production of recombinant antigens and antibodies in Nicotiana benthamiana using ‘magnifection’ technology: GMP-compliant facilities for small- and large-scale manufacturing. Curr Top Microbiol Immunol. 2010;375:127–154.
  • Dugdale B, Mortimer CL, Kato M, et al. In plant activation: an inducible, hyperexpression platform for recombinant protein production in plants. Plant Cell. 2013;25(7):2429–2443.
  • Arntzen C. Plant-made pharmaceuticals: from ‘Edible Vaccines’ to Ebola therapeutics. Plant Biotechnol J. 2015;13(8):1013–1016.
  • Tusé D, Tu T, McDonald KA. Manufacturing economics of plant-made biologics: case studies in therapeutic and industrial enzymes. Biomed Res Int. 2014;2014:256135.
  • Ritacco FV, Wu Y, Khetan A. Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: history, key components, and optimization strategies. Biotechnol Prog. 2018;34(6):1407–1426.
  • Sanchez-Garcia L, Martin L, Mangues R, et al. Recombinant pharmaceuticals from microbial cells: a 2015 update. Microb Cell Fact. 2016;15:33.
  • Sivakumar G, Ed. New insights into cell culture technology. Rijeka, Croatia: InTech; 2017. p. 43–97.
  • Shaaltiel Y, Bartfeld D, Hashmueli S, et al. Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher’s disease using a plant cell system. Plant Biotechnol J. 2007;5(5):579–590.
  • Shaaltiel Y, Gingis-Velitski S, Tzaban S, et al. Plant-based oral delivery of β-glucocerebrosidase as an enzyme replacement therapy for Gaucher’s disease. Plant Biotechnol J. 2007;13(8):1033–1040.
  • Qiu X, Wong G, Audet J, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014;514(7520):47–53.
  • Yusibov V, Kushnir N, Streatfield S. Antibody production in plants and Green Algae. Annu Rev Plant Biol. 2016;67:669–701.

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