Edible plants for oral delivery of biopharmaceuticals

British Journal of Clinical Pharmacology

Volumn 83, Issue 1, 2017, Pages 71-81

  Merlin, Matilde ^a   Pezzotti, Mario ^a   Avesani, Linda ^a  

^a UNIVERSITY OF VERONA   (Italy)

Author keywords

edible plant; molecular farming; oral delivery; oral tolerance; transgenic plants; vaccine

Indexed keywords

HERBACEOUS AGENT; VACCINE; EDIBLE VACCINE; PLANT PROTEIN; RECOMBINANT PROTEIN;

ARTICLE; DRUG DELIVERY SYSTEM; DRUG MECHANISM; EDIBLE PLANT; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; IMMUNOLOGICAL TOLERANCE; MOLECULAR FARMING; MUCOSAL IMMUNITY; NONHUMAN; PRIORITY JOURNAL; VACCINATION; CHEMISTRY; DRUG EFFECTS; GENETICS; IMMUNOLOGY; ORAL DRUG ADMINISTRATION; PHARMACEUTICS; PROCEDURES;

ADMINISTRATION, ORAL; BIOPHARMACEUTICS; DRUG DELIVERY SYSTEMS; HUMANS; IMMUNITY, MUCOSAL; PLANT PROTEINS; PLANTS, EDIBLE; RECOMBINANT PROTEINS; VACCINES, EDIBLE;

EID: 84968608614     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/bcp.12949     Document Type: Article

References (82)

1. Merlin M, Gecchele E, Capaldi S, Pezzotti M, Avesani L. Comparative evaluation of recombinant protein production in different biofactories: the green perspective. Biomed Res Int 2014; 2014: 136 419.
2. Hensel G, Floss DM, Arcalis E, Sack M, Melnik S, Altmann F, et al. Transgenic production of an anti HIV antibody in the barley endosperm. PLoS One 2015; 10: e0140476.
3. Mbewana S, Mortimer E, Pêra FF, Hitzeroth II, Rybicki EP. Production of H5N1 influenza virus matrix protein two ectodomain protein bodies in tobacco plants and in insect cells as a candidate universal influenza vaccine. Front Bioeng Biotechnol 2015; 3: 197.
4. Bundó M, Montesinos L, Izquierdo E, Campo S, Mieulet D, Guiderdoni E, et al. Production of cecropin A antimicrobial peptide in rice seed endosperm. BMC Plant Biol 2014; 14: 102.
5. Tinazzi E, Merlin M, Bason C, Beri R, Zampieri R, Lico C, et al. Plant-derived chimeric virus particles for the diagnosis of primary Sjögren syndrome. Front Plant Sci 2015; 6: 1080.
6. Yoon S, Devaiah SP, Choi SE, Bray J, Love R, Lane J et al. Over-expression of the cucumber expansin gene (Cs-EXPA1) in transgenic maize seed for cellulose deconstruction. Transgenic Res 2016; 25: 173–86.
7. Bohmert-Tatarev K, McAvoy S, Daughtry S, Peoples OP, Snell KD. High levels of bioplastic are produced in fertile transplastomic tobacco plants engineered with a synthetic operon for the production of polyhydroxybutyrate. Plant Physiol 2011; 155: 1690–708.
8. Yao J, Weng Y, Dickey A, Wang KY. Plants as factories for human pharmaceuticals: applications and challenges. Int J Mol Sci 2015; 16: 28 549–65.
9. Chan HT, Daniell H. Plant-made oral vaccines against human infectious diseases-Are we there yet? Plant Biotechnol J 2015; 13: 1056–70.
10. Menkhaus TJ, Bai Y, Zhang C, Nikolov ZL, Glatz CE. Considerations for the recovery of recombinant proteins from plants. Biotechnol Prog 2004; 20: 1001–14.
11. Streatfield SJ, Lane JR, Brooks CA, Barker DK, Poage ML, Mayor JM, et al. Corn as a production system for human and animal vaccines. Vaccine 2003; 21: 812–5.
12. Kwon KC, Daniell H. Low-cost oral delivery of protein drugs bioencapsulated in plant cells. Plant Biotechnol J 2015; 13: 1017–22.
13. Lai H, Chen Q. Bioprocessing of plant-derived virus-like particles of Norwalk virus capsid protein under current Good Manufacture Practice regulations. Plant Cell Rep 2012; 31: 573–84.
14. Merlin M, Gecchele E, Arcalis E, Remelli S, Brozzetti A, Pezzotti M et al. Enhanced GAD65 production in plants using the MagnICON transient expression system: optimization of upstream production and downstream processing. Biotechnol J 2015; Dec 28. doi: 10.1002/biot.201500187
15. Cheung SC, Liu LZ, Lan LL, Liu QQ, Sun SS, Chan JC, et al. Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies. BMC Biotechnol 2011; 11: 37.
16. 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.
17. 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.
18. Tacket CO, Pasetti MF, Edelman R, Howard JA, Streatfield S. Immunogenicity of recombinant LT-B delivered orally to humans in transgenic corn. Vaccine 2004; 22: 4385–9.
19. Kapusta J, Modelska A, Pniewski T, Figlerowicz M, Jankowski K, Lisowa O, et al. Oral immunization of human with transgenic lettuce expressing hepatitis B surface antigen. Adv Exp Med Biol 2001; 495: 299–303.
20. Fukuda K, Ishida W, Harada Y, Wakasa Y, Takagi H, Takaiwa F, et al. Prevention of allergic conjunctivitis in mice by a rice-based edible vaccine containing modified Japanese cedar pollen allergens. Br J Ophthalmol 2015; 99: 705–9.
21. Sherman A, Su J, Lin S, Wang X, Herzog RW, Daniell H. 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: 1659–68.
22. Ma SW, Zhao DL, Yin ZQ, Mukherjee R, Singh B, Qin HY, et al. Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance. Nat Med 1997; 3: 793–6.
23. Schillberg S, Raven N, Fischer R, Twyman RM, Schiermeyer A. Molecular farming of pharmaceutical proteins using plant suspension cell and tissue cultures. Curr Pharm Des 2013; 19: 5531–42.
24. Twyman RM, Schillberg S, Fischer R. Optimizing the yield of recombinant pharmaceutical proteins in plants. Curr Pharm Des 2013; 19: 5486–94.
25. Haq TA, Mason HS, Clements JD, Arntzen CJ. Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 1995; 268: 714–6.
26. Soria-Guerra RE, Rosales-Mendoza S, Moreno-Fierros L, López-Revilla R, Alpuche-Solís AG. Oral immunogenicity of tomato-derived sDPT polypeptide containing Corynebacterium diphtheriae, Bordetella pertussis and Clostridium tetani exotoxin epitopes. Plant Cell Rep 2011; 30: 417–24.
27. Daniell H, Kumar S, Dufourmantel N. Breakthrough in chloroplast genetic engineering of agronomically important crops. Trends Biotechnol 2005; 23: 238–45.
28. Porceddu A, Falorni A, Ferradini N, Cosentino A, Calcinaro F, Faleri C, et al. Transgenic plants expressing humanglutamic acid decarboxylase (GAD65), a major autoantigen ininsulin-dependent diabetes mellitus. Mol Breed 1999; 5: 553–60.
29. Azegami T, Yuki Y, Kiyono H. Challenges in mucosal vaccines for the control of infectious diseases. Int Immunol 2014; 26: 517–28.
30. Kashima K, Yuki Y, Mejima M, Kurokawa S, Suzuki Y, Minakawa S et al. Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants. Plant Cell Rep 2016; 35: 667–79.
31. Mason HS, Warzecha H, Mor T, Arntzen CJ. Edible plant vaccines: applications for prophylactic and therapeutic molecular medicine. Trends Mol Med 2002; 8: 324–9.
32. Trivedi PK, Nath P. MaExpl, an ethylene-induced ex- pansin from ripening banana fruit. Plant Sci 2004; 167: 1351–8.
33. Chan HT, Chia MY, Pang VF, Jeng CR, Do YY, Huang PL. Oral immunogenicity of porcine reproductive and respiratory syndrome virus antigen expressed in transgenic banana. Plant Biotechnol J 2013; 11: 315–24.
34. Tacket CO. Plant-based oral vaccines: results of human trials. Curr Top Microbiol Immunol 2009; 332: 103–17.
35. Butelli E, Titta L, Giorgio M, Mock HP, Matros A, Peterek S, et al. Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors. Nat Biotechnol 2008; 26: 1301–8.
36. Juárez P, Presa S, Espí J, Pineda B, Antón MT, Moreno V, et al. Neutralizing antibodies against rotavirus produced in transgenically labelled purple tomatoes. Plant Biotechnol J 2012; 10: 341–52.
37. Moog F. The lining of the small intestine. Sci Am 1981; 245: 154–58 (160, 162 et passiom).
38. Weiner HL, da Cunha AP, Quintana F, Wu H. Oral tolerance. Immunol Rev 2011; 241: 241–59.
39. Weiner HL. Oral tolerance, an active immunologic process mediated by multiple mechanisms. J Clin Invest 2000; 106: 935–7.
40. Wang X, Sherman A, Liao G, Leong KW, Daniell H, Terhorst C, et al. Mechanism of oral tolerance induction to therapeutic proteins. Adv Drug Deliv Rev 2013; 65: 759–73.
41. Brandtzaeg P. Mucosal immunity: induction, dissemination, and effector functions. Scand J Immunol 2009; 70: 505–15.
42. Rosales-Mendoza S, Salazar-González JA. Immunological aspects of using plant cells as delivery vehicles for oral vaccines. Expert Rev Vaccines 2014; 13: 737–49.
43. Pasetti MF, Simon JK, Sztein MB, Levine MM. Immunology of gut mucosal vaccines. Immunol Rev 2011; 239: 125–48.
44. Gebril A, Alsaadi M, Acevedo R, Mullen AB, Ferro VA. Optimizing efficacy of mucosal vaccines. Expert Rev Vaccines 2012; 11: 1139–55.
45. Hernández M, Rosas G, Cervantes J, Fragoso G, Rosales-Mendoza S, Sciutto E. Transgenic plants: a 5-year update on oral antipathogen vaccine development. Expert Rev Vaccines 2014; 13: 1523–36.
46. Kwon KC, Verma D, Singh ND, Herzog R, Daniell H. Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells. Adv Drug Deliv Rev 2013; 65: 782–99.
47. Arcalis E, Stadlmann J, Rademacher T, Marcel S, Sack M, Altmann F, et al. Plant species and organ influence the structure and subcellular localization of recombinant glycoproteins. Plant Mol Biol 2013; 83: 105–17.
48. Huang L, Ikejiri A, Shimizu Y, Adachi T, Goto Y, Toyama J, et al. Immunoadjuvant activity of crude lectin extracted from Momordica charantia seed. J Vet Med Sci 2008; 70: 533–5.
49. Petrovsky N. Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity. Vaccine 2006; 24 (Suppl 2): S2–26-9.
50. Sparg SG, Light ME, van Staden J. Biological activities and distribution of plant saponins. J Ethnopharmacol 2004; 94: 219–43.
51. Bosch D, Schots A. Plant glycans: friend or foe in vaccine development? Expert Rev Vaccines 2010; 9: 835–42.
52. Gregory JA, Topol AB, Doerner DZ, Mayfield S. Alga-produced cholera toxin-Pfs25 fusion proteins as oral vaccines. Appl Environ Microbiol 2013; 79: 3917–25.
53. Gorantala J, Grover S, Rahi A, Chaudhary P, Rajwanshi R, Sarin NB, et al. Generation of protective immune response against anthrax by oral immunization with protective antigen plant-based vaccine. J Biotechnol 2014; 176: 1–10.
54. Rosales-Mendoza S, Soria-Guerra RE, Moreno-Fierros L, Govea-Alonso DO, Herrera-Díaz A, Korban SS, et al. Immunogenicity of nuclear-encoded LTB:ST fusion protein from Escherichia coli expressed in tobacco plants. Plant Cell Rep 2011; 306: 1145–52.
55. Soh HS, Chung HY, Lee HH, Ajjappala H, Jang K, Park JH, et al. Expression and functional validation of heat-labile enterotoxin B (LTB) and cholera toxin B (CTB) subunits in transgenic rice (Oryza sativa). Springerplus 2015; 4: 148.
56. Hayden CA, Fischer ME, Andrews BL, Chilton HC, Turner DD, Walker JH, et al. Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses. Vaccine 2015; 33: 2881–6.
57. Gonzalez-Rabade N, McGowan EG, Zhou F, McCabe MS, Bock R, Dix PJ, et al. Immunogenicity of chloroplast-derived HIV-1 p24 and a p24-Nef fusion protein following subcutaneous and oral administration in mice. Plant Biotechnol J 2011; 9: 629–38.
58. Yuki Y, Mejima M, Kurokawa S, Hiroiwa T, Takahashi Y, Tokuhara D, et al. Induction of toxin-specific neutralizing immunity by molecularly uniform rice-based oral cholera toxin B subunit vaccine without plant-associated sugar modification. Plant Biotechnol J 2013; 11: 799–808.
59. Yuki Y, Mejima M, Kurokawa S, Hiroiwa T, Kong IG, Kuroda M, et al. RNAi suppression of rice endogenous storage proteins enhances the production of rice-based Botulinum neutrotoxin type A vaccine. Vaccine 2012; 30: 4160–6.
60. Mardanova ES, Kotlyarov RY, Kuprianov VV, Stepanova LA, Tsybalova LM, Lomonosoff GP, et al. Rapid high-yield expression of a candidate influenza vaccine based on the ectodomain of M2 protein linked to flagellin in plants using viral vectors. BMC Biotechnol 2015; 15: 42.
61. Avesani L, Bortesi L, Santi L, Falorni A, Pezzotti M. Plant-made pharmaceuticals for the prevention and treatment of autoimmune diseases: where are we? Expert Rev Vaccines 2010; 9: 957–69.
62. Su J, Zhu L, Sherman A, Wang X, Lin S, Kamesh 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.
63. Verma D, Moghimi B, LoDuca PA, Singh HD, Hoffman BE, Herzog RW, et al. Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice. Proc Natl Acad Sci U S A 2010; 107: 7101–6.
64. Su J, Sherman A, Doerfler PA, Byrne BJ, Herzog RW, Daniell H. Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice. Plant Biotechnol J 2015; 13: 1023–32.
65. Lee CC, Ho H, Lee KT, Jeng ST, Chiang BL. Construction of a Der p2-transgenic plant for the alleviation of airway inflammation. Cell Mol Immunol 2011; 8: 404–14.
66. Suzuki K, Kaminuma O, Yang L, Takai T, Mori A, Umezu-Goto M, 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: 982–90.
67. Wakasa Y, Takagi H, Watanabe N, Kitamura N, Fujiwara Y, Ogo Y, et al. Concentrated protein body product derived from rice endosperm as an oral tolerogen for allergen-specific immunotherapy–a new mucosal vaccine formulation against Japanese cedar pollen allergy. PLoS One 2015; 10: e0120209.
68. DeVane LC. Principles of pharmacokinetics and pharmacodynamics. In: Schatzberg AF, Nemeroff CB, eds. The American Physiatrics Publishing Text-Book of Psychopharmacology, third ed. Washington, DC: American Psychiatric Publishing, pp. 181–200.
69. Marx M. Watching peptide drugs grow up. Chem Eng News 2005; 83: 17–24.
70. Lindh I, Bråve A, Hallengärd D, Hadad R, Kalbina I, Strid Å, et al. Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses. Vaccine 2014; 32: 2288–93.
71. Rubio-Infante N, Govea-Alonso DO, Romero-Maldonado A, García-Hernández AL, Ilhuicatzi-Alvarado D, Salazar-González JA, et al. A Plant-Derived Multi-HIV Antigen Induces Broad Immune Responses in Orally Immunized Mice. Mol Biotechnol 2015; 57: 662–74.
72. Hongli L, Xukui L, Ting L, Wensheng L, Lusheng S, Jin Z. Transgenic tobacco expressed HPV16-L1 and LT-B combined immunization induces strong mucosal and systemic immune responses in mice. Hum Vaccin Immunother 2013; 9: 83–9.
73. Monroy-García A, Gómez-Lim MA, Weiss-Steider B, Hernández-Montes J, Huerta-Yepez S, Rangel-Santiago JF, et al. Immunization with an HPV-16 L1-based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model. Arch Virol 2014; 159: 291–305.
74. Yang Y, Li X, Yang H, Qian Y, Zhang Y, Fang R, et al. Immunogenicity and virus-like particle formation of rotavirus capsid proteins produced in transgenic plants. Sci China Life Sci 2011; 54: 82–9.
75. Tokuhara D, Álvarez B, Mejima M, Hiroiwa T, Takahashi Y, Kurokawa S, et al. Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection. J Clin Invest 2013; 123: 3829–38.
76. Rukavtsova EB, Rudenko NV, Puchko EN, Zakharchenko NS, Buryanov YI. Study of the immunogenicity of hepatitis B surface antigen synthesized in transgenic potato plants with increased biosafety. J Biotechnol 2015; 203: 84–8.
77. Nahampun HN, Bosworth B, Cunnick J, Mogler M, Wang K. Expression of H3N2 nucleoprotein in maize seeds and immunogenicity in mice. Plant Cell Rep 2015; 34: 969–80.
78. Lee C, Kim HH, Choi KM, Chung KW, Choi YK, Jang MJ, et al. Murine immune responses to a Plasmodium vivax-derived chimeric recombinant protein expressed in Brassica napus. Malar J 2011; 10: 106.
79. Del L, Yácono M, Farran I, Becher ML, Sander V, Sánchez VR, et al. A chloroplast-derived Toxoplasma gondii GRA4 antigen used as an oral vaccine protects against toxoplasmosis in mice. Plant Biotechnol J 2012; 10: 1136–44.
80. Albarracín RM, Becher ML, Farran I, Sander VA, Corigliano MG, Yácono ML, et al. The fusion of Toxoplasma gondii SAG1 vaccine candidate to Leishmania infantum heat shock protein 83-kDa improves expression levels in tobacco chloroplasts. Biotechnol J 2015; 10: 748–59.
81. Uvarova EA, Belavin PA, Permyakova NV, Zagorskaya AA, Nosareva OV, Kakimzhanova AA, et al. Oral immunogenicity of plant-made Mycobacterium tuberculosis ESAT6 and CFP10. Biomed Res Int 2013; 2013: 316 304.
82. Zhang Y, Chen S, Li J, Liu Y, Hu Y, Cai H. Oral immunogenicity of potato-derived antigens to Mycobacterium tuberculosis in mice. Acta Biochim Biophys Sin (Shanghai) 2012; 44: 823–30.