Implications of plant glycans in the development of innovative vaccines

Expert Review of Vaccines

Volumn 15, Issue 7, 2016, Pages 915-925

  Rosales Mendoza, Sergio ^a   Salazar González, Jorge A ^a   Decker, Eva L ^b   Reski, Ralf ^b  

^a UNIVERSIDAD AUTÓNOMA DE SAN LUIS POTOSÍ   (Mexico)

^b UNIVERSITY OF FREIBURG   (Germany)

Author keywords

adjuvant; amylosomes; bacterial polysaccharides; conjugate vaccines; delta inulin; glyco engineering; immunogenicity; Molecular pharming; pectin; starch

Indexed keywords

ANTIGEN; BETA GLUCAN; DELTA INULIN; DEXTRAN; GLYCAN; GLYCOPROTEIN; IMMUNOLOGICAL ADJUVANT; INULIN; MANNAN; OLIGOSACCHARIDE; PECTIN; POLYSACCHARIDE; STARCH; UNCLASSIFIED DRUG; VACCINE; DRUG CARRIER;

APOPLAST; BIOSYNTHESIS; DRUG DELIVERY SYSTEM; DRUG DESIGN; GENETIC ENGINEERING; IMMUNOSTIMULATION; MOLECULAR FARMING; NONHUMAN; PHYSCOMITRELLA PATENS; PLANT CELL; PRIORITY JOURNAL; REVIEW; SEED PLANT; VACCINE PRODUCTION; ANIMAL; CHEMISTRY; HUMAN; ISOLATION AND PURIFICATION; PLANT;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; DRUG CARRIERS; HUMANS; PLANTS; POLYSACCHARIDES;

EID: 84961213249     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/14760584.2016.1155987     Document Type: Review

References (140)

1. B.Pulendran, J.Z.Oh, H.I.Nakaya, et al. Immunity to viruses: learning from successful human vaccines. Immunol Rev. 2013;255:243–255.
2. S.Thomas, B.A.Luxon Vaccines based on structure-based design provide protection against infectious diseases. Expert Rev Vaccines. 2013;12:1301–1311.
3. N.Petrovsky, P.D.Cooper. Carbohydrate-based immune adjuvants. Expert Rev Vaccines. 2011;10:523–537.
4. C.Mukherjee, K.Mäkinen, J.Savolainen, et al. Chemistry and biology of oligovalent β-(1→2)-linked oligomannosides: new insights into carbohydrate-based adjuvants in immunotherapy. Chemistry. 2013;19:7961–7974.
5. M.Heidelberger, O.T.Avery. The soluble specific substance of pneumococcus. J Exp Med. 1923;38:73–79.• Historic research on discovery of pneumococcal carbohydrates.
6. M.Dalziel, M.Crispin, C.N.Scanlan, et al. Emerging principles for the therapeutic exploitation of glycosylation. Science. 2014;343:1235681.
7. C.C.Liu, X.S.Ye. Carbohydrate-based cancer vaccines: target cancer with sugar bullets. Glycoconj J. 2012;29:259–271.
8. J.Heimburg-Molinaro, M.Lum, G.Vijay, et al. Cancer vaccines and carbohydrate epitopes. Vaccine. 2011;29:8802–8826.
9. Food and drugs administration (FDA). PneumoVax approval; [cited 2015 Aug5]. Available from: http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM257088.pdf
10. S.Aljunid, G.Abuduxike, Z.Ahmed, et al. Impact of routine PCV7 (Prevenar) vaccination of infants on the clinical and economic burden of pneumococcal disease in Malaysia. BMC Infect Dis. 2011;11:248.
11. A.A.Palmu, J.Jokinen, D.Borys, et al. Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial. Lancet. 2013;381:214–222.
12. K.S.Reisinger, R.Baxter, S.L.Block, et al. Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra. Clin Vaccine Immunol. 2009;16:1810–1815.
13. L.C.Marcus, J.E.Froeschle, D.R.Hill, et al. Safety of Typhim Vi vaccine in a postmarketing observational study. J Travel Med. 2007;14:386–391.
14. Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61:816–819.
15. L.Deng, D.L.Kasper, T.P.Krick, et al. Characterization of the linkage between the type III capsular polysaccharide and the bacterial cell wall of group B Streptococcus. J Biol Chem. 2000;275:7497–7504.
16. A.Coutinho, G.Moller. B cell mitogenic properties of thymus-independent antigens. Nature New Biol. 1973;245:12–14.
17. D.J.Barrett. Human immune responses to polysaccharide antigens: an analysis of bacterial polysaccharide vaccines in infants. Adv Pediatr. 1985;32:139–158.
18. R.K.Sood, A.Fattom. Capsular polysaccharide–protein conjugate vaccines and intravenous immunoglobulins. Expert Opin Investig Drugs. 1998;7:333–347.
19. C.J.Lee, L.H.Lee, S.Lu, et al. Bacterial polysaccharides as vaccines – immunity and chemical characterization. Adv Exp Med Biol. 2001;491:453–471.
20. J.P.Watt, L.J.Wolfson, K.L.O’Brien, et al. Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet. 2009;374:903–911.
21. World Health Organization (WHO). Global Immunization Data; 2014 [cited 2015 Aug5]. Available from: http://www.who.int/immunization/monitoring_surveillance/Global_Immunization_Data.pdf
22. World Health Organization (WHO). Pneumonia fact sheet N°331; [cited 2015 Aug5]. Available from: http://www.who.int/mediacentre/factsheets/fs331/en/
23. N.G.Rouphael, D.S.Stephens. Neisseria meningitidis: biology, microbiology, and epidemiology. Methods Mol Biol. 2012;799:1–20.
24. L.H.Harrison, C.L.Trotter, M.E.Ramsay. Global epidemiology of meningococcal disease. Vaccine. 2009;27(Suppl 2):B51–B63.
25. Centers for Disease Control and Prevention. Meningococcal disease: technical & clinical information; 2014 [cited 2015 Aug5]. Available from: http://www.cdc.gov/meningococcal/clinical-info.html
26. Centers for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease—United States, 1998–2003; [cited 2015 Nov25]. Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5436a1.htm
27. C.M.Wernette, C.E.Frasch, D.Madore, et al. Enzyme linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides. Clin Diagn Lab Immunol. 2003;10:514–519.
28. D.B.Wu, N.Chaiyakunapruk, H.Y.Chong, et al. Choosing between 7-, 10- and 13-valent pneumococcal conjugate vaccines in childhood: a review of economic evaluations (2006–2014). Vaccine. 2015;33:1633–1658.
29. I.Jantan, W.Ahmad, S.N.Bukhari. Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. Front Plant Sci. 2015;6:655.
30. S.K.Mazmanian, D.L.Kasper. The love–hate relationship between bacterial polysaccharides and the host immune system. Nat Rev Immunol. 2006;6:849–858.
31. D.Guillén, S.Moreno-Mendieta, R.Pérez, et al. Starch granules as a vehicle for the oral administration of immobilized antigens. Carbohydr Polym. 2014;112:210–215.•• Highlights the potential of starch as a delivery vehicle of oral vaccines.
32. G.G.van de Wijdeven, H.J.Hirschberg, W.Weyers, et al. Phase 1 clinical study with Bioneedles, a delivery platform for biopharmaceuticals. Eur J Pharm Biopharm. 2015;89:126–133.• Describes the clinical evaluation of a delivery vehicle based on starch.
33. J.P.Amorij, V.Saluja, A.H.Petersen, et al. Pulmonary delivery of an inulin-stabilized influenza subunit vaccine prepared by spray-freeze drying induces systemic, mucosal humoral as well as cell-mediated immune responses in BALB/c mice. Vaccine. 2007;25:8707–8717.
34. J.Hütter, B.Lepenies. Carbohydrate-based vaccines: an overview. Methods Mol Biol. 2015;1331:1–10.
35. Y.L.Huang, C.Y.Wu. Carbohydrate-based vaccines: challenges and opportunities. Expert Rev Vaccines. 2010;9:1257–1274.• Presents a background on the general use of carbohydrates as vaccine targets.
36. V.Yusibov, S.J.Streatfield, N.Kushnir. Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond. Hum Vaccin. 2011;7:313–321.
37. Y.Shaaltiel, S.Gingis-Velitski, S.Tzaban, et al. Plant-based oral delivery of β-glucocerebrosidase as an enzyme replacement therapy for Gaucher’s disease. Plant Biotechnol J. 2015;13:1033–1040.•• Shows the potential for achieving the oral delivery of biopharmaceuticals using plant cells.
38. C.M.Smith, S.C.Fry, K.C.Gough, et al. Recombinant plants provide a new approach to the production of bacterial polysaccharide for vaccines. PLoS One. 2014;9:e88144.•• A pioneering report on the production of bacterial polysaccharides in plant species through genetic engineering.
39. Y.van Kooyk, G.A.Rabinovich. Protein-glycan interactions in the control of innate and adaptive immune responses. Nat Immunol. 2008;9:593–601.
40. J.E.Hudak, C.R.Bertozzi. Glycotherapy: new advances inspire a reemergence of glycans in medicine. Chem Biol. 2014;21:16–37.•• Review containing outstanding clinical results on glycotherapy and glycoengineering.
41. N.W.Palm, R.Medzhitov. Pattern recognition receptors and control of adaptive immunity. Immunol Rev. 2009;227:221–233.
42. C.A.Janeway, R.Medzhitov. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.
43. A.M.Stephen. Other plant polysaccharides. In: G.O.Aspinall, editor. The polysaccharides. Vol. 2. New York (NY): Academic Press; 1983. p. 97–193.
44. P.D.Cooper, M.Carter. Anti-complementary action of polymorphic “solubility forms” of particulate inulin. Mol Immunol. 1986;23:895–901.
45. P.D.Cooper, E.J.Steele. The adjuvanticity of gamma inulin. Immunol Cell Bio. 1988;66:345–352.
46. P.D.Cooper, M.Carter. The anti-melanoma activity of inulin in mice. Mol Immunol. 1986;23:903–908.
47. P.D.Cooper, E.J.Steele. Algammulin, a new vaccine adjuvant comprising γ inulin particles containing alum: preparation and in vitro properties. Vaccine. 1991;9:351–357.
48. P.D.Cooper, R.Turner, J.McGovern. Algammulin (γ inulin/alum hybrid adjuvant) has greater adjuvanticity than alum for hepatitis B surface antigen in mice. Immunol Lett. 1991;27:131–134.
49. N.Petrovsky. Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity. Vaccine. 2006;24(Suppl 2):26–29.
50. P.D.Cooper, N.Petrovsky. Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2->1] poly(fructo-furanosyl) α-D-glucose polymers. Glycobiology. 2011;21:595–606.•• Describes the production of delta inulin and its adjuvant activity.
51. M.Lobigs, M.Pavy, R.A.Hall, et al. An inactivated Vero cell-grown Japanese encephalitis vaccine formulated with Advax, a novel inulin-based adjuvant, induces protective neutralizing antibody against homologous and heterologous flaviviruses. J Gen Virol. 2010;91:1407–1417.
52. Y.Honda-Okubo, F.Saade, N.Petrovsky. Advax™, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses. Vaccine. 2012;30:5373–5381.
53. F.Saade, Y.Honda-Okubo, S.Trec, et al. A novel hepatitis B vaccine containing Advax™, a polysaccharide adjuvant derived from delta inulin, induces robust humoral and cellular immunity with minimal reactogenicity in preclinical testing. Vaccine. 2013;31:1999–2007.
54. H.Bielefeldt-Ohmann, N.A.Prow, W.Wang, et al. Safety and immunogenicity of a delta inulin-adjuvanted inactivated Japanese encephalitis virus vaccine in pregnant mares and foals. Vet Res. 2014;45:130.
55. D.Gordon, P.Kelley, S.Heinzel, et al. Immunogenicity and safety of Advax™, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: a randomized controlled Phase 1 study. Vaccine. 2014;32:6469–6477.•• Contains the data on the clinical evaluation of a vaccine adjuvanted with inulin.
56. Y.Honda-Okubo, C.H.Ong, N.Petrovsky. Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single-dose influenza vaccine protection. Vaccine. 2015;33:4892–4900.• Shows the efficacy of inulin as a potent vaccine adjuvant.
57. S.Thiel, M.Gadjeva. Humoral pattern recognition molecules: mannan-binding lectin and ficolins. Adv Exp Med Biol. 2009;653:58–73.
58. K.C.Sheng, D.S.Pouniotis, M.D.Wright, et al. Mannan derivatives induce phenotypic and functional maturation of mouse dendritic cells. Immunology. 2006;118:372–383.
59. J.Stambas, G.Pietersz, I.McKenzie, et al. Oxidised mannan as a novel adjuvant inducing mucosal IgA production. Vaccine. 2002;20:1068–1078.
60. O.Proudfoot, S.Esparon, C.K.Tang, et al. Mannan adjuvants intranasally administered inactivated influenza virus in mice rendering low doses inductive of strong serum IgG and IgA in the lung. BMC Infect Dis. 2015;15:101.•• Novel promising research on intranasal mannan-adjuvant influenza vaccine.
61. G.G.van de Wijdeven. Development and assessment of mini projectiles as drug carriers. J Control Release. 2002;85:145–162.
62. H.J.Hirschberg, G.G.van de Wijdeven, H.Kraan, et al. Bioneedles as alternative delivery system for hepatitis B vaccine. J Control Release. 2010;147:211–217.
63. P.C.Soema, G.J.Willems, K.van Twillert, et al. Solid bioneedle-delivered influenza vaccines are highly thermostable and induce both humoral and cellular immune responses. PLoS One. 2014;9:e92806.• Highlights the advantages of using starch-based materials for immunization.
64. H.Kraan, I.Ploemen, G.van de Wijdeven, et al. Alternative delivery of a thermostable inactivated polio vaccine. Vaccine. 2015;33:2030–2037.
65. D.Christensen, T.Lindenstrøm, G.van de Wijdeven, et al. Syringe free vaccination with CAF01 adjuvated Ag85B-ESAT-6 in Bioneedles provides strong and prolonged protection against tuberculosis. PLoS One. 2010;5:e15043.
66. H.J.Hirschberg, G.G.van de Wijdeven, A.B.Kelder, et al. Bioneedles as vaccine carriers. Vaccine. 2008;26:2389–2397.
67. D.N.Bolam, A.Ciruela, S.McQueen-Mason, et al. Pseudomonas cellulose-binding domains mediate their effects by increasing enzyme substrate proximity. Biochem J. 1998;331:775–781.
68. R.Rodriguez Sanoja, J.Morlon-Guyot, J.Jore, et al. Comparative characterization of complete and truncated forms of Lactobacillus amylovorus alpha-amylase and role of the C-terminal direct repeats in raw-starch binding. Appl Environ Microbiol. 2000;66:3350–3356.
69. D.Guillén, S.Moreno-Mendieta, P.Aguilera, et al. The starch-binding domain as a tool for recombinant protein purification. Appl Microbiol Biotechnol. 2013;97:4141–4148.
70. S.A.Moreno-Mendieta, D.Guillén, C.Espitia, et al. A novel antigen-carrier system: the Mycobacterium tuberculosis Acr protein carried by raw starch microparticles. Int J Pharm. 2014;474:241–248.
71. D.Dauvillée, S.Delhaye, S.Gruyer, et al. Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules. PLoS One. 2010;5:e15424.• Describes a potential approach for producing in vivo amylosomes, which are highly immunogenic starch–antigen complexes.
72. C.A.Hayden, M.E.Fischer, B.L.Andrews, et al. Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses. Vaccine. 2015;33:2881–2886.
73. S.J.Streatfield, J.R.Lane, C.A.Brooks, et al. Corn as a production system for human and animal vaccines. Vaccine. 2003;21:812–815.
74. F.Takaiwa, Y.Wakasa, H.Takagi, et al. Rice seed for delivery of vaccines to gut mucosal immune tissues. Plant Biotechnol J. 2015;13:1041–1055.
75. T.Moravec, M.A.Schmidt, E.M.Herman, et al. Production of Escherichia coli heat labile toxin (LT) B subunit in soybean seed and analysis of its immunogenicity as an oral vaccine. Vaccine. 2007;25:1647–1657.
76. L.C.Hudson, R.Garg, K.L.Bost, et al. Soybean seeds: a practical host for the production of functional subunit vaccines. Biomed Res Int. 2014;2014:340804.
77. R.Hevey, C.C.Ling. Recent advances in developing synthetic carbohydrate-based vaccines for cancer immunotherapies. Future Med Chem. 2012;4:545–584.
78. C.Anish, B.Schumann, C.L.Pereira, et al. Chemical biology approaches to designing defined carbohydrate vaccines. Chem Biol. 2014;21:38–50.• Describes the state of the art in producing glycan targeting vaccines.
79. T.F.Carson, W.D.Maclay. The acetylation of polyuronides with formamides as a dispersing agent. J Am Chem Soc. 1946;68:1015–1017.
80. B.Szewczyk, A.Taylor. Immunochemical properties of Vi antigen from Salmonella typhi Ty2: presence of two antigenic determinants. Infect Immun. 1980;29:539–544.
81. S.C.Szu, S.Bystricky, M.Hinojosa-Ahumada, et al. Synthesis and some immunologic properties of an O-acetyl pectin [poly(1–>4)-alpha-D-GalpA]-protein conjugate as a vaccine for typhoid fever. Infect Immun. 1994;62(12):5545–5549.• Describes the immunogenic properties of a pectin-based immunogen.
82. M.Landy. Studies in Vi antigen. VI. Immunization of human beings with purified Vi antigen. Am J Hyg. 1954;60:52–62.
83. Z.Kossaczka, S.Bystricky, D.A.Bryla, et al. Synthesis and immunological properties of Vi and di-O-acetyl pectin protein conjugates with adipic acid dihydrazide as the linker. Infect Immun. 1997;65:2088–2093.
84. S.C.Szu, K.F.Lin, S.Hunt, et al. Phase I clinical trial of O-acetylated pectin conjugate, a plant polysaccharide based typhoid vaccine. Vaccine. 2014;32:2618–2622.•• A relevant example on how a plant glycan, pectin, may serve as precursor of immunogens.
85. R.Bock. Engineering chloroplasts for high-level foreign protein expression. Methods Mol Biol. 2014;1132:93–106.
86. J.A.Salazar-González, B.Bañuelos-Hernández, S.Rosales-Mendoza. Current status of viral expression systems in plants and perspectives for oral vaccines development. Plant Mol Biol. 2015;87:203–217.
87. Y.Y.Gleba, D.Tusé, A.Giritch. Plant viral vectors for delivery by Agrobacterium. Curr Top Microbiol Immunol. 2014;375:155–192.
88. R.Reski, J.Parsons, E.L.Decker. Moss-made pharmaceuticals: from bench to bedside. Plant Biotechnol J. 2015;13:1191–1198.• Contains a compilation of the biopharmaceuticals produced in moss.
89. Y.Wakasa, H.Takagi, N.Watanabe, 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.
90. D.O.Govea-Alonso, G.A.Cardineau, S.Rosales-Mendoza. Principles of plant-based vaccines. In: S.Rosales-Mendoza, editor. Genetically engineered plants as a source of vaccines against wide spread diseases - an integrated view. New York (NY): Springer Science Business Media; 2014. p. 1–14.
91. Y.Shaaltiel, D.Bartfeld, S.Hashmueli, 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;5:579–590.
92. X.Qiu, G.Wong, J.Audet, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014;514:47–53.
93. G.M.Lyon, A.K.Mehta, J.B.Varkey, et al. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med. 2014;371:2402–2409.
94. M.McCarthy. US signs contract with ZMapp maker to accelerate development of the Ebola drug. BMJ. 2014;349:g5488.
95. M.Bendandi, S.Marillonnet, R.Kandzia, et al. Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma. Ann Oncol. 2010;21(12):2420–2427.
96. N.Landry, S.Pillet, D.Favre, et al. Influenza virus-like particle vaccines made in Nicotiana benthamiana elicit durable, poly-functional and cross-reactive T cell responses to influenza HA antigens. Clin Immunol. 2014;154:164–177.•• Describes an example of a plant-made vaccine in an advanced degree of development.
97. C.Jin, F.Altmann, R.Strasser, et al. A plant-derived human monoclonal antibody induces an anti-carbohydrate immune response in rabbits. Glycobiology. 2008;18:235–241.
98. B.J.Ward, N.Landry, S.Trépanier, et al. Human antibody response to N-glycans present on plant-made influenza virus-like particle (VLP) vaccines. Vaccine. 2014;32:6098–6106.
99. R.Strasser, J.Stadlmann, M.Schähs, et al. Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol J. 2008;6:392–402.
100. A.Castilho, P.Gattinger, J.Grass, et al. N-glycosylation engineering of plants for the biosynthesis of glycoproteins with bisected and branched complex N-glycans. Glycobiology. 2011;21:813–823.
101. M.Schähs, R.Strasser, J.Stadlmann, et al. Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnol J. 2007;5:657–663.
102. A.Castilho, L.Neumann, S.Daskalova, et al. Engineering of sialylated mucin-type O-glycosylation in plants. J Biol Chem. 2012;287:36518–36526.
103. A.Hohe, R.Reski. Optimisation of a bioreactor culture of the moss Physcomitrella patens for mass production of protoplasts. Plant Sci. 2002;163:69–74.
104. R.Reski, W.O.Abel. Induction of budding on chloronemata and caulonemata of the moss, Physcomitrella patens, using isopentenyladenine. Planta. 1985;165:354–358.
105. A.Lucumi, C.Posten, M.N.Pons. Image analysis supported moss cell disruption in photo-bioreactors. Plant Biol. 2005;7:276–282.
106. A.Lucumi, C.Posten. Establishment of long-term perfusion cultures of recombinant moss in a pilot tubular photobioreactor. Process Biochem. 2006;41:2180–2187.
107. M.Cerff, C.Posten. Enhancing the growth of Physcomitrella patens by combination of monochromatic red and blue light – a kinetic study. Biotechnol J. 2012;7:527–536.
108. G.Schween, T.Egener, D.Fritzkowsky, et al. Large-scale analysis of 73,329 Physcomitrella plants transformed with different gene disruption libraries: production parameters and mutant phenotypes. Plant Biol. 2005;7:228–237.
109. D.G.Schaefer, J.Zrÿd, C.D.Knight, et al. Stable transformation of the moss Physcomitrella patens. Mol Gen Genet. 1991;226:418–424.
110. A.Hohe, T.Egener, J.M.Lucht, et al. An improved and highly standardised transformation procedure allows efficient production of single and multiple targeted gene knockouts in a moss, Physcomitrella patens. Curr Genet. 2004;44:339–347.
111. A.Koprivova, C.Stemmer, F.Altmann, et al. Targeted knockouts of Physcomitrella lacking plant-specific immunogenic N-glycans. Plant Biotechnol J. 2004;2:517–523.
112. J.Parsons, F.Altmann, C.K.Arrenberg, et al. Moss-based production of asialo-erythropoietin devoid of Lewis A and other plant-typical carbohydrate determinants. Plant Biotechnol J. 2012;10:851–861.
113. C.M.Huether, O.Lienhart, A.Baur, et al. Glyco-engineering of moss lacking plant-specific sugar residues. Plant Biol. 2005;7:292–299.
114. J.Parsons, F.Altmann, M.Graf, et al. A gene responsible for prolyl-hydroxylation of moss-produced recombinant human erythropoietin. Sci Rep. 2013;3:3019.
115. A.Büttner-Mainik, A.Parsons, H.Jérome, et al. Production of biologically active recombinant human factor H in Physcomitrella. Plant Biotechnol J. 2011;9:373–383.
116. L.Orellana-Escobedo, S.Rosales-Mendoza, A.Romero-Maldonado, et al. An Env-derived multi-epitope HIV chimeric protein produced in the moss Physcomitrella patens is immunogenic in mice. Plant Cell Rep. 2014;34:425–433.
117. S.Rosales-Mendoza, L.Orellana-Escobedo, A.Romero-Maldonado, et al. The potential of Physcomitrella patens as a platform for the production of plant-based vaccines. Expert Rev Vaccines. 2014;13:203–212.•• Analyzes the implications of Physcomitrella patens as a convenient platform for vaccine production.
118. S.Debolt, J.M.Estevez. Current challenges in plant cell walls: editorial overview. Front Plant Sci. 2012;3:232.
119. D.J.Cosgrove, M.C.Jarvis. Comparative structure and biomechanics of plant primary and secondary cell walls. Front Plant Sci. 2012;3:204.
120. A.W.Roberts, J.T.Bushoven. The cellulose synthase (CESA) gene superfamily of the moss Physcomitrella patens. Plant Mol Biol. 2007;63:207–219.
121. I.Moller, I.Sørensen, A.J.Bernal, et al. High-throughput mapping of cell-wall polymers within and between plants using novel microarrays. Plant J. 2007;50:1118–1128.
122. C.Arrecubieta, E.Garcia, R.Lopez. Demonstration of UDP-glucose dehydrogenase activity in cell extracts of Escherichia coli expressing the pneumococcal cap3A gene required for the synthesis of type 3 capsular polysaccharide. J Bacteriol. 1996;178:2971–2974.
123. H.Jennings. Capsular polysaccharides as human vaccine. Adv Carbo Chem. 1983;41:155–208.
124. R.Kunze, W.B.Frommer, U.I.Flugge. Metabolic engineering of plants: the role of membrane transport. Metab Eng. 2002;4:57–66.
125. S.C.Sharples, S.C.Fry. Radioisotope ratios discriminate between competing pathways of cell wall polysaccharide and RNA biosynthesis in living plant cells. Plant J. 2007;52:252–262.
126. M.Wacker, M.F.Feldman, N.Callewaert, et al. Substrate specificity of bacterial oligosaccharyltransferase suggests a common transfer mechanism for the bacterial and eukaryotic systems. Proc Natl Acad Sci USA. 2006;103:7088–7093.
127. M.Kowarik, N.M.Young, S.Numao, et al. Definition of the bacterial N-glycosylation site consensus sequence. EMBO Journal. 2006;25:1957–1966.
128. J.A.Iwashkiw, M.A.Fentabil, A.Faridmoayer, et al. Exploiting the Campylobacter jejuni protein glycosylation system for glycoengineering vaccines and diagnostic tools directed against brucellosis. Microb Cell Fact. 2012;11:13.
129. J.Cuccui, R.M.Thomas, M.G.Moule, et al. Exploitation of bacterial N-linked glycosylation to develop a novel recombinant glycoconjugate vaccine against Francisella tularensis. Open Biol. 2013;3:130002.
130. J.Ihssen, M.Kowarik, S.Dilettoso, et al. Production of glycoprotein vaccines in Escherichia coli. Microb Cell Fact. 2010;9:61.•• A pioneering report on the production of conjugated vaccinesin vivo.
131. M.Wetter, M.Kowarik, M.Steffen, et al. Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component. Glycoconj J. 2013;30:511–522.
132. M.M.Kämpf, M.Braun, D.Sirena, et al. In vivo production of a novel glycoconjugate vaccine against Shigella flexneri 2a in recombinant Escherichia coli: identification of stimulating factors for in vivo glycosylation. Microb Cell Fact. 2015;14:12.
133. S.Rosales-Mendoza, M.A.Tello-Olea. Carrot cells: a pioneering platform for biopharmaceuticals production. Mol Biotechnol. 2015;57:219–232.
134. J.K.Ma, J.Drossard, D.Lewis, et al. Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants. Plant Biotechnol J. 2015;13:1106–1120.
135. M.Sack, T.Rademacher, H.Spiegel, et al. From gene to harvest: insights into upstream process development for the GMP production of a monoclonal antibody in transgenic tobacco plants. Plant Biotechnol J. 2015;13:1094–1105.
136. N.Mohagheghpour, M.Dawson, P.Hobbs, et al. Glucans as immunological adjuvants. Adv Exp Med Biol. 1995;383:13–22.
137. H.Huang, G.R.Ostroff, C.K.Lee, et al. Robust stimulation of humoral and cellular immune responses following vaccination with antigen-loaded β-glucan particles. MBio. 2010;1:e00164–10.
138. J.Kaistha, J.Sokhey, S.Singh, et al. Adjuvant effect of DEAE-dextran and tetanus toxoid on whole cell heat inactivated phenol preserved typhoid vaccine. Indian J Pathol Microbiol. 1996;39:287–292.
139. E.M.Bachelder, T.T.Beaudette, K.E.Broaders, et al. In vitro analysis of acetylated dextran microparticles as a potent delivery platform for vaccine adjuvants. Mol Pharm. 2010;7:826–835.
140. S.V.Popov, Y.S.Ovodov. Polypotency of the immunomodulatory effect of pectins. Biochemistry (Mosc). 2013;78:823–835.