Is an oral plant-based vaccine against hepatitis B virus possible?

Current Pharmaceutical Biotechnology

Volumn 13, Issue 15, 2012, Pages 2692-2704

  Pniewski, Tomasz ^a  

^a INSTITUTE OF PLANT GENETICS   (Poland)

Author keywords

Anti HBV vaccine; HBsAg; Mucosal immunisation; Oral immunisation; Oral tolerance; Oral vaccines; Plant based vaccines

Indexed keywords

HEPATITIS A HEPATITIS B VACCINE; HEPATITIS B ANTIGEN; HEPATITIS B VACCINE; HEPATITIS VACCINE; PLANT MEDICINAL PRODUCT; RECOMBINANT HEPATITIS B VACCINE;

ARTICLE; DRUG COST; FREEZE DRYING; HEPATITIS B; HEPATITIS B VIRUS; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOGENICITY; INTESTINE LYMPHATIC TISSUE; NONHUMAN; POTATO; PROTEIN PURIFICATION; PUBLIC HEALTH PROBLEM; TOBACCO;

ADMINISTRATION, ORAL; ANIMALS; HEPATITIS B; HEPATITIS B SURFACE ANTIGENS; HUMANS; IMMUNE TOLERANCE; IMMUNIZATION, SECONDARY; PLANTS; VACCINATION;

HEPATITIS B VIRUS;

EID: 84872557085     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/138920112804724837     Document Type: Article

References (107)

1. Hilleman, M.R. Critical overview and outlook: pathogenesis, prevention, and treatment of hepatitis and hepatocarcinoma caused by hepatitis B virus. Vaccine, 2003, 21, 4626-4649.
2. WHO Media Centre. Hepatitis B. http://www.who.int/mediacentre/ factsheets/fs204/en/ (revised August 2008).
3. Krugman, S. The newly licensed hepatitis B vaccine. Characteristics and indications for use. JAMA, 1982, 247, 2012-2015.
4. McAleer, W.J.; Buynak, E.B.; Maigetter, R.Z. Human hepatitis B vaccine from recombinant yeast. Nature, 1984, 307, 178-180.
5. Goldstein, S.T.; Fiore, A.E. Toward the global elimination of hepatitis B virus transmission. J. Pediatr., 2001, 139, 343-345.
6. Michel, M.-L.; Tiollais, P. Hepatitis B vaccines: Protective efficacy and therapeutic potential. Pathol. Biol. 2010, 58, 288-295.
7. Shepard, C.W.; Simard E.P.; Finelli, L.; Fiore, A.E.; Bell, B.P. Hepatitis B Virus Infection: Epidemiology and Vaccination. Epidemiol. Rev., 2006, 28, 112-125.
8. Kew, M.C. Epidemiology of chronic hepatitis B virus infection, hepatocellular carcinoma, and hepatitis B virus-induced hepatocellular carcinoma. Pathol. Biol., 2010, 58, 273-277.
9. Romano, L.; Paladini, S.; Van Damme, P.; Zanetti, A.R. The worldwide impact on the control and protection of viral hepatitis B. Dig. Liver Dis., 2011, 43S, S2-S7.
10. Hilleman, M.R. Overview of the pathogenesis, prophylaxis and therapeutics of viral hepatitis B, with focus on reduction to practical applications. Vaccine, 2001 19, 1837-1848.
11. Yuen, M.-F.; Lai, C.-L. Treatment of chronic hepatitis B: Evolution over two decades. J. Gastroenterol. Hepatol., 2011, 26(Suppl. 1), 138-143.
12. Hollinger, F.B. Hepatitis B Virus. In: Fields Virology; Fields, B.N.; Knipe, D.M.; Howley, P.M. et al. Eds.; Lippincott-Raven Publishers: Philadelphia, 1996, pp. 2739-2806.
13. Cooreman, M.P.; Leroux-Roels, G.; Paulij, W.P. Vaccine-and hepatitis B immune globulin-induced escape mutations of hepatitis B virus surface antigen. J. Biomed. Sci., 2001, 8, 237-247.
14. Huang, X.; Lu, D.; Ji, G.; Sun, Y.; Ma, L.; Chen, Z.; Zhang, L.; Huang, J.; Yu, L. Hepatitis B virus (HBV) vaccine-induced escape mutants of HBV S gene among children from Qidong area, China. Virus Res., 2004, 99, 63-68.
15. Liaw, Y.F.; Sung, J.J.; Chow, W.C.; Farrell, G.; Lee, C.Z.; Yuen, H.; Tanwandee, T.; Tao, Q.M.; Shue, K.; Keene, O.N.; Dixon, J.S.; Gray, D.F.; Sabbat, J. Lamivudine for patients with chronic hepatitis B and advanced liver disease, N. Engl. J. Med., 2004, 351, 1521-1531.
16. Young, M.D.; Rosenthal, M.H.; Dickson, B.; Du, W.; Maddrey, W.C. A multi-center controlled study of rapid hepatitis B vaccination using a novel triple antigen recombinant vaccine. Vaccine, 2001, 19, 3437-3443.
17. Singh N.P.; Mandal, S.K.; Thakur, A.; Kapoor, D.; Anuradha, S.; Prakash, A.; Kohli, R.; Agarwal, S.K. Efficacy of GM-CSF as an adjuvant to hepatitis B vaccination in patients with chronic renal failure-results of a prospective, randomized trial. Ren. Fail., 2003, 25, 255-266
18. Bruss, V. Hepatitis B virus morphogenesis. World J. Gastroenterol., 2007, 13, 65-73.
19. Blanchet, M.; Sureau, C. Infectivity determinants of the Hepatitis B Virus pre-S domain are confined to the N-Terminal 75 amino acid residues. J. Virol., 2007, 81, 5841-5849.
20. Madaliński, K.; Sylvan, S.P.; Hellstrom, U.; Mikoėajewicz, J.; Zembrzuska-Sadkowska, E.; Piontek, E. Antibody responses to preS components after immunisation of children with low doses of BioHepB. Vaccine, 2002, 20, 92-97.
21. Rendi-Wagner, P.; Shouval, D.; Genton, B.; Lurie, Y.; Rümke, H.; Boland, G.; Cerny, A.; Heim, M.; Bach, D.; Schroeder, M.; Kollaritsch, H.; Comparative immunogenecity of a PreS/S hepatitis B vaccine in non-and low responders to conventional vaccine. Vaccine, 2006, 24, 2781-2789.
22. Brocke, P.; Schaefer, S.; Melber, K.; Jenzelewski, V.; Müller, F.; Dahlems, U.; Bartelsen, O.; Park, K.-N.; Janowicz, Z.A.; Gellissen, G. Recombinant Hepatitis B vaccines: disease characterization and vaccine production. In: Production of Recombinant Proteins. Novel Microbial and Eukaryotic Systems; Gellissen, G. Ed.; Wiley-VCH Verlag GmbH & Co KGaA: Weinheim, 2005, pp. 319-359.
23. Aziz, M.A.; Midcha, S.; Waheed, S.M.; Bhatnagar, R. Oral vaccines: new needs, new possibilities. BioEssays, 2007, 29, 591-604.
24. Mestecky, J.; Nguyen, H.; Czerkinsky, C.; Kiyono, H.; Oral immunisation: An update. Curr. Opin. Gastroen., 2008, 24, 713-719.
25. Wang, L.; Coppel, R.L. Oral vaccine delivery: can it protect against non-mucosal pathogens? Expert Rev. Vaccines, 2008, 7, 729-738.
26. Langridge, W.H. Edible vaccines. Sci. Am., 2000, 283, 66-71.
27. Streatfield, S.J. Mucosal immunisation using recombinant plantbased oral vaccines. Methods, 2006, 38, 150-157.
28. Daniell, H.: Singh, N.D.; Mason, H.; Streatfield, S.J. Plant-made vaccine antigens and biopharmaceuticals. Trends Plant Sci., 2009, 14, 669-679.
29. Brandtzaeg, P. Role of secretory antibodies in the defence against infections. Int. J. Med. Microbiol., 2003, 293, 3-15.
30. Mowat, A.M. Anatomical basis of tolerance and immunity to intestinal antigens. Nature Rev., 2003, 3, 331-341.
31. Brandtzaeg, P. Induction of secretory immunity and memory at mucosal surfaces. Vaccine, 2007, 25, 5467-5484.
32. Koprowski, H.; Jervis, G.A.; Norton, T.W. Immune responses in human volunteers upon oral administration of a rodent-adapted strain of poliomyelitis virus. Am. J. Hyg., 1952, 55, 108-126.
33. Skene, C.D.; Sutton, P. Saponin-adjuvanted particulate vaccines for clinical use. Methods, 2006, 40, 53-59.
34. Vajdy, M. Immunomodulatory properties of vitamins, flavonoids and plant oils and their potential as vaccine adjuvants and delivery systems. Expert Opin. Biol. Ther., 2011, 11, 1501-1513.
35. Mason, H.S.; Lam, D.M.-K.; Arntzen, C.J. Expression of hepatitis B surface antigen in transgenic plants. Proc. Natl. Acad. Sci. USA, 1992, 89, 11745-11749.
36. Thanavala, Y.; Yang, Y.-F.; Lyons, P.; Mason, H.S.; Arntzen, C.J. Immunogenicity of transgenic plant-derived hepatitis B surface antigen. Proc. Natl. Acad. Sci. USA, 1995, 92, 3358-3361.
37. Kapusta, J.; Modelska, A.; Figlerowicz, M.; Pniewski, T.; Letellier, M.; Lisowa, O.; Yusibov, V.; Koprowski, H.; Plucienniczak, A.; Legocki, A.B. A plant-derived edible vaccine against hepatitis B virus. FASEB J., 1999, 13, 1796-1799.
38. Rukavtsova, E.B.; Zolova, O.E.; Buryanova, N. Ya.; Borisova, V.N.; Bykov, V.A.; Buryanov, Ya.I. Analysis of Transgenic Tobacco Plants Carrying the Gene for the Surface Antigen of the Hepatitis B Virus. Genetika, 2003, 39, 51-56.
39. Sunil Kumar, G.B.; Srinivas, L.; Ganapathi, T.R.; Bapat, V.A. Hepatitis B surface expression in transgenic tobacco (Nicotiana tabacum) plants using four different expression cassettes. Plant Cell Tiss. Org. Cult., 2006, 84, 315-323.
40. Ehsani, P.; Khabiri, A.; Domansky, N.N. Polypeptides of hepatitis B surface antigen produced in transgenic potato. Gene, 1997, 190, 107-111.
41. Shulga, N. Ya.; Rukavtsova, E.B.; Krymsky, M.A.; Borisova, V.N.; Melnikov, V.A.; Bykov, V.A.; Buryanov, Ya.I. Expression and Characterization of Hepatitis B Surface Antigen in Transgenic Potato Plants. Biochemistry (Moscow), 2004, 69, 1158-1164.
42. Zhao, C.H.; Wang, R.; Zhao, C.S.; Wang, G.L., Tian, P. Expression of human HBV surface antigen gene with and without preS in transgenic tomato. Nongye Shengwu Jishu Xubao, 2000, 8, 85-88.
43. Chen, H.Y.; Zhang, J.; Gao, Y.; Du, H.L.; Ma, Y.; Zheng, W.Z.; Xia, N.S. Transforming HBsAg into peanut and detection of its immunogenecity. Lett. Biotechnol., 2002, 4, 245-250.
44. Peng, J.; Song, Q.; Chengkui, T. Expression of hepatitis B surface antigen gene (HBsAg) in Laminaria japonica (Laminariales, Phaeophyta). Chin. Sci. Bull., 2002, 17, 1438-1440.
45. Sunil Kumar, G.B.; Ganapathi, T.R.; Srinivas, L.; Revathi, C.J.; Bapat, V.A. Expression of hepatitis B surface antigen in potato hairy roots. Plant Sci., 2006, 170, 918-925.
46. Pniewski, T.; Kapusta, J.; Pžucienniczak, A. Agrobacterium tumefaciens-mediated transformation of yellow lupin to generate callus tissue producing surface antigen of HBV in a long-term culture. J. Appl. Genet., 2006, 47, 309-318.
47. Imani, J.; Berting, A.; Nitsche, S.; Schaefer, S.; Gerlich, W.H.; Neumann, K.-H. The integration of a major hepatitis B virus gene into cell-cycle synchronized carrot cell suspension cultures and its expression in regenerated carrot plants. Plant Cell Tiss. Org. Cult., 2002, 71, 157-164.
48. Sunil Kumar, G.B.; Ganapathi, T.R.; Revathi, C.J.; Prasad, K.S.N.; Bapat, V.A. Expression of hepatitis B surface antigen in transgenic banana plants and NT-1 cell line of tobacco. BARC News Lett., 2003, 237, 85-96.
49. Sunil Kumar, G.B.; Ganapathi, T.R.; Revathi, C.J.; Prasad, K.S.N.; Bapat, V.A. Expression of hepatitis B surface antigen in tobacco cell suspension cultures. Prot. Exp. Purif., 2003, 32, 10-17.
50. Sunil Kumar, G.B.; Ganapathi, T.R.; Srinivas, L.; Revathi, C.J.; Bapat, V.A. Secretion of hepatitis B surface antigen in transformed tobacco cell suspension cultures. Biotechnol. Lett., 2005, 27, 927-932.
51. Ganapathi, T. R.; Sunil Kumar, G.B.; Srinivas, L.; Revathi, C.J.; Bapat, V.A. Analysis of the limitations of hepatitis B surface antigen expression in soybean cell suspension cultures. Plant Cell Rep., 2007, 1575-1584.
52. Dogan, B.; Mason, H.S.; Richter, L.; Hunter, J.B.; Shuler, M.L. Process options in hepatitis B surface antigen extraction from transgenic potato. Biotechnol. Prog., 2000, 16, 435-441.
53. Sunil Kumar, G.B.; Ganapathi, T.R.; Revathi, C.J.; Srinivas, L.; Bapat, V.A. Expression of hepatitis B surface antigen in transgenic banana plants. Planta, 2005, 222, 484-493
54. Smith, M.L.; Mason, H.S.; Shuler, M.L. Hepatitis B surface antigen (HBsAg) expression in plant cell culture: kinetics of antigen accumulation in batch culture and its intracellular form. Biotechnol. Bioeng., 2002, 80, 812-822.
55. Lam, D. M.-K.; Arntzen, C.J. Vaccines produced and administered through edible plants. U.S. Patent 5,484,719, January 16, 1996.
56. Sojikul. P.; Buehner, N.; Mason, H.S. A plant signal peptidehepatitis B surface antigen fusion protein with enhanced stability and immunogenicity expressed in plant cells. Proc. Natl. Acad. Sci. USA, 2003, 100, 2209-2214.
57. Huang, Z.; Mason, H.S. Conformational analysis of hepatitis B surface antigen fusions in an Agrobacterium-mediated transient expression system. Plant Biotechnol. J., 2004, 2, 241-249.
58. Huang, Z.; Elkin, G.; Maloney, B.J.; Buehner, N.; Arntzen, C.J.; Thanavala, Y.; Mason, H.S. Virus-like particles expression and assembly in plants: hepatitis B and Norwalk viruses. Vaccine, 2005, 23, 1851-1858.
59. Huang, Z.; LePore, K.; Elkin, G.; Thanavala, Y.; Mason, H.S. High-yield rapid production of hepatitis B surface antigen in plant leaf by a viral expression system. Plant Biotechnol. J., 2008, 6, 202-209.
60. Richter, L.J.; Thanavala, Y.; Arntzen, C.J.; Mason, H.S. Production of hepatitis B surface antigen in transgenic plants for oral immunisation. Nat. Biotechnol., 2000, 18, 1167-1171.
61. Kong, Q.; Richter, L.; Yang, Y.F.; Arntzen, C.J.; Mason, H.S.; Thanavala, Y. Oral immunisation with hepatitis B surface antigen expressed in transgenic plants. Proc. Natl. Acad. Sci. USA, 2001, 98, 11539-11544.
62. Mason, H.S.; Thanavala, Y.; Arntzen, C.J.; Richter, E. Expression of immunogenic hepatitis B surface antigen in transgenic plants. U.S. Patent 6,551,820 B1, April 22, 2003.
63. Gao, Y.; Ma, Y.; Li, M.; Cheng, T.; Li, S.-W.; Zhang, J.; Xia, N.-S. Oral immunisation of animals with transgenic cherry tomatillo expressing HBsAg. World J. Gastroenterol., 2003, 9, 996-1002.
64. Thanavala, Y.; Mahoney, M.; Pal, S.; Scott, A.; Richter, L.; Natarajan, N.; Goodwin, P.; Arntzen, C.J.; Mason, H.S. Immunogenicity in humans of an edible vaccine for hepatitis B. Proc. Natl. Acad. Sci. USA, 2005, 102, 3378-3382.
65. Kapusta, J.; Modelska, A.; Figlerowicz, M.; Pniewski, T.; Lisowa, O.; Koprowski, H.; Pžucienniczak, A.; Legocki, A.B. Plant-based edible vaccine against HBV. Immunology Lett., 2000, 73, 269.
66. Kapusta, J.; Modelska, A.; Pniewski, T.; Figlerowicz, M.; Jankowski, K.; Lisowa, O.; Plucienniczak, A.; Koprowski, H.; Legocki, A.B. Oral immunisation of human with transgenic lettuce expressing hepatitis B surface antigen. Adv. Exp. Med. Biol., 2001, 495, 299-303.
67. Pniewski, T.; Kapusta, J.; Bocičg, P.; Wojciechowicz, J.; Kostrzak, A.; Gdula, M.; Fedorowicz-Strońska, O.; Wójcik, P.; Otta, H.; Samardakiewicz, S.; Wolko, B.; Pžucienniczak, A. Low-dose oral immunisation with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation. J. Appl. Genet., 2011, 52, 125-136.
68. Salyaev, R.K.; Rekoslavskaya, N.I.; Stolbikov, A.S.; Hammond, R.W.; Shchelkunov, S.N. Synthesis of Hepatitis B Virus surface antigen in tomato plants transgenic for the preS2-S gene. Doklady Biochem. Biophys., 2007, 416, 290-293.
69. Salyaev, R.K.; Stolbikov, A.S.; Rekoslavskaya, N.I.; Shchelkunov, S.N.; Pozdnyakov, S.G.; Chepinoga, A.V.; Hammond, R.V. Obtaining tomato plants transgenic for the preS2-S-HDEL gene, which synthesize the major hepatitis B surface antigen. Doklady Biochem. Biophys., 2010, 433, 187-190.
70. Pniewski, T.; Kapusta, J.; Bocičg, P.; Kostrzak, A.; Fedorowicz-Strońska, O.; Czyů, M., Gdula, M.; Krajewski, P.; Wolko, B.; Pžucienniczak, A. Plant expression, lyophilisation and storage of HBV medium and large surface antigens for a prototype oral vaccine formulation. Plant Cell Rep., 2012, 31, 585-595.
71. Joung, Y.H.; Youm, J.-W.; Jeon, J.H.; Lee, B.C.; Ryu, C.J.; Hong, H.J.; Kim, H.C.; Joung, H.; Kim, H.S. Expression of the hepatitis B surface S and preS2 antigens in tubers of Solanum tuberosum. Plant Cell Rep., 2004, 22, 925-930.
72. Youm, J.-W.; Won, Y.-S.; Jeon, J.H.; Ryu, C.J.; Choi, Y.-K.; Kim, H.-C.; Kim, B.-D.; Joung, H.; Kim, H.S. Oral immunogenicity of potato-derived HBsAg middle protein in BALB/c mice. Vaccine, 2007, 25, 577-584.
73. Lou, X.-M.; Yao, Q.-H.; Zhang, Z.; Peng, R.-H.; Xiong, A.-S.; Wang, H.-K. (2007) Expression of the human Hepatitis B Virus large surface antigen gene in transgenic tomato plants. Clin. Vaccine Immunol., 2007, 14, 464-469.
74. Imamura, T.; Araki, M.; Miyanohara, A.; Nakao, J.; Yonemura, H.; Ohtomo, N.; Matsubara, K. (1987) Expression of hepatitis B virus middle and large surface antigen genes in Saccharomyces cerevisiae. J. Virol., 1987, 61, 3543-3549.
75. Gleba, Y.; Klimyuk, V.; Marillonnet, S. Magnifection-a new platform for expressing recombinant vaccines in plants. Vaccine, 2005, 23, 2042-2048.
76. Streatfield, S. Oral hepatitis B vaccine candidates produced and delivered in plant material. Immunol. Cell Biol., 2005, 83, 257-262.
77. Streatfield, S.J.; Jilka, J.M.; Hood, E.E.; Turner, D.D.; Bailey, M.R.; Mayor, J.M.; Woodard, S.L.; Beifuss, K.K.; Horn, M.E.; Delaney, D.E.; Tizard, I.R.; Howard, J.A. Plant-based vaccines: unique advantages. Vaccine, 2001, 19, 2742-2748.
78. Arakawa, T.; Chong, D.K.X.; Langridge, W.H.R. Efficacy of a food plant-based oral cholera toxin subunit vaccine. Nat. Biotechnol., 1998, 16, 292-297.
79. Williamson, E.; Westrich, G.M.; Viney J.L. Modulating dendritic cells to optimize mucosal immunisation protocols. J. Immunol., 1999, 163, 3668-3675.
80. Kapusta, J.; Pniewski, T.; Bocičg, P.; Wojciechowicz, J.; Pžucienniczak, A. Nanogram doses of alum-adjuvanted HBs antigen induce humoral immune response in mice when orally administered. Arch. Immunol. Ther. Exp., 2010, 58, 143-151.
81. Pamer, E.G. Immune responses to commensal and environmental microbes. Nat. Immunol., 2007, 8, 1173-1178.
82. Richman, L.K.; Chiller, J.M.; Brown, W.R.; Hanson, D.G.; Vaz, N.M. Enterically induced immunologic tolerance. I. Induction of suppressor T lymphocytes by intragastric administration of soluble proteins. J. Immunol., 1978, 121, 2429-2434.
83. Li, T.; Takeda, N.; Miyamura, T. Oral administration of hepatitis E virus-like particles induces a systemic and mucosal immune response in mice. Vaccine, 2001, 19, 3476-3484.
84. Yao, Q.; Zhang, R.; Guo, L.; Li, M.; Chen, C. The cell-independent immune responses to chimeric hemagglutinin/simian human immunodeficiency virus-like particles vaccine. J. Immunol., 2004, 173, 1951-1958.
85. Matzinger, P. Tolerance, danger and extended family. Annu. Rev. Immunol., 1994, 12, 991-1045.
86. Kirk, D.D.; McIntosh, K.; Walmsley, A.M.; Peterson, R.K.D. Risk analysis for plant-made vaccines. Transgenic Res., 2005, 14, 449-462.
87. Mestecky, J.; Russell, M.W.; Elson, C.O. Perspectives on mucosal vaccines: is mucosal tolerance a barrier? J. Immunol., 2007, 179, 5633-5638.
88. Taams, L.S.; van Rensen, A.J.; Poelen, M.C.; van Els, C.A.; Besseling, A.C.; Wagenaar, J.P.; van Eden, W.; Wauben, M.H. Anergic T cells actively suppress T cell responses via the antigenpresenting cell. Eur. J. Immunol., 1998, 28, 2902-2912.
89. Friedman, A.; Weiner, H.L. Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proc. Natl. Acad. Sci. USA, 1994, 91, 6688-6692.
90. Chen, Y.; Inobe, J.; Marks, R.; Gonnella, P.; Kuchroo, V.K.; Weiner, H.L. Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature, 1995, 376, 177-180; erratum, Nature, 1995, 377, 257.
91. Heath, W.R.; Carbone, F.R. Cross-presentation, dendritic cells, tolerance and immunity. Annu. Rev. Immunol., 2001, 19, 47-64.
92. Swarbrick, E.T.; Stokes, C.R.; Soothill, J.F. Absorption of antigens after oral immunisation and the simultaneous induction of specific systemic tolerance. Gut, 1979, 20, 121-125.
93. Garside, P.; Mowat, A.M. Oral tolerance. Semin. Immunol., 2001, 13, 177-185.
94. Gotsman, I.; Beinart, R.; Alper, R.; Rabbani, E.; Engelhardt, D.; Ilan, Y. Induction of oral tolerance towards hepatitis B envelope antigens in a murine model. Antiviral Res., 2000, 48, 17-26.
95. Strobel, S. Immunity induced after a feed of antigen during early life: oral tolerance v. sensitization. Proc. Nutr. Soc., 2001, 60, 437-442.
96. Beyer, A.J.; Wang, K.; Umble, A.N.; Wolt, J.D.; Cunnick, J.E. Low-dose exposure and immunogenicity of transgenic maize expressing the Escherichia coli heat-labile toxin B subunit. Environ. Health. Persp., 2007, 115, 354-360.
97. Borges, O.; Tavares, J.; de Sousa, A.; Borchard, G.; Junginger, H.E.; Cordeiro-da-Silva, A. Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles. Eur. J. Pharm. Sci., 2007, 32, 278-290.
98. Shukla, A.; Khatri, K.; Gupta, P.N.; Goyal, A.K.; Mehta, A.; Vyas, S.P. Oral immunisation against hepatitis B using bile salt stabilized vesicles (bilosomes). J. Pharm. Pharm. Sci., 2008, 11, 59-66.
99. Kostrzak, A.; Cervantes Gonzales, M.; Guetard, D.; Nagaraju, D.B.; Wain-Hobson, S.; Tepfer, D.; Pniewski, T.; Sala, M. Oral administration of low doses of plant-based HBsAg induced antigen-specific IgAs and IgGs in mice, without increasing levels of regulatory T cells. Vaccine, 2009, 27, 4798-4807.
100. Sunil Kumar, G.B.; Ganapathi, T.R.; Bapat, V.A. Production of hepatitis B surface antigen in recombinant plant systems: an update. Biotechnol. Prog., 2007, 23, 532-539.
101. Komarova, T.V.; Baschieri, S.; Donini, M.; Marusic, C.; Benvenuto, E.; Dorokhov, Y.L. Transient expression systems for plant-derived biopharmaceuticals. Expert Rev. Vaccines, 2010, 9, 859-876.
102. Takahashi, I.; Nochi, T.; Yuki, Y.; Kiyono, H. New horizon of mucosal immunity and vaccines. Curr. Opin. Immunol., 2009, 21, 352-358.
103. Diminsky, D.; Moav, N.; Gorecki, M.; Barenholz, Y. Physical, chemical and immunological stability of CHO-derived hepatitis B surface antigen (HBs Ag) particles. Vaccine, 2000, 18, 3-17.
104. Rosales-Mendoza, S.; Alpuche-Solís, A.G.; Soria-Guerra, R.E.; Moreno-Fierros, L.; Martínez-González, L.; Herrera-Díaz, A.; Korban, S.S. Expression of an Escherichia coli antigenic fusion protein comprising the heat labile toxin B subunit and the heat stable toxin, and its assembly as a functional oligomer in transplastomic tobacco plants. Plant J., 2009, 57, 45-54.
105. Wee, J.L.; Scheerlinck, J.P.; Snibson, K.J.; Edwards, S.; Pearse, M.; Quinn, C.; Sutton, P. Pulmonary delivery of ISCOMATRIX influenza vaccine induces both systemic and mucosal immunity with antigen dose sparing. Mucosal Immunol, 2008, 1, 489-496; erratum Mucosal Immunol., 2009, 2, 184.
106. Tiwari, S; Verma, P. C; Singh, P.K.; Tuli, R. Plants as bioreactors for the production of vaccine antigens. Biotechnol. Adv., 2011, 27, 449-467.
107. Bosch, D.; Schots, A. Plant glycans: friend or foe in vaccine development? Expert Rev. Vaccines, 2010, 9, 835-842.