Production of dengue virus envelope protein domain III-based antigens in tobacco chloroplasts using inducible and constitutive expression systems

Plant Molecular Biology

Volumn 91, Issue 4-5, 2016, Pages 497-512

  Gottschamel, Johanna ^a,b   Lössl, Andreas ^b   Ruf, Stephanie ^c   Wang, Yanliang ^a   Skaugen, Morten ^d   Bock, Ralph ^c   Clarke, Jihong Liu ^a  

^a NORWEGIAN INSTITUTE OF BIOECONOMY RESEARCH   (Norway)

^b UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES   (Austria)

^c MAX PLANCK INSTITUTE OF MOLECULAR PLANT PHYSIOLOGY   (Germany)

^d NORWEGIAN UNIVERSITY OF LIFE SCIENCES   (Norway)

Author keywords

Chloroplast transformation; Dengue virus; EDIII antigen; Plant produced vaccine; Tobacco

Indexed keywords

ALCOHOL; RECOMBINANT PROTEIN; VIRUS ANTIGEN; VIRUS ENVELOPE PROTEIN;

AMINO ACID SEQUENCE; BIOSYNTHESIS; CHEMISTRY; CHLOROPLAST; DENGUE VIRUS; GENE VECTOR; GENETIC PROCEDURES; GENETICS; IMMUNOLOGY; METABOLISM; PROTEIN DOMAIN; REGENERATION; TOBACCO; TRANSGENIC PLANT;

AMINO ACID SEQUENCE; ANTIGENS, VIRAL; CHLOROPLASTS; DENGUE VIRUS; ETHANOL; GENETIC TECHNIQUES; GENETIC VECTORS; PLANTS, GENETICALLY MODIFIED; PROTEIN DOMAINS; RECOMBINANT PROTEINS; REGENERATION; TOBACCO; VIRAL ENVELOPE PROTEINS;

EID: 84976334315     PISSN: 01674412     EISSN: 15735028     Source Type: Journal    
DOI: 10.1007/s11103-016-0484-5     Document Type: Article

References (118)

1. Apel W, Schulze WX, Bock R (2010) Identification of protein stability determinants in chloroplasts. Plant J 63:636–650. doi:10.1111/j.1365-313X.2010.04268.x
2. Arora U, Tyagi P, Swaminathan S, Khanna N (2013) Virus-like particles displaying envelope domain III of dengue virus type 2 induce virus-specific antibody response in mice. Vaccine 31:873–878. doi:10.1016/j.vaccine.2012.12.016
3. Bally J, Nadai M, Vitel M, Rolland A, Dumain R, Dubald M (2009) Plant physiological adaptations to the massive foreign protein synthesis occurring in recombinant chloroplasts. Plant Physiol 150:1474–1481. doi:10.1104/pp.109.139816
4. Batra G, Chaudhry S, Hapugoda M, Khanna N, Swaminathan S (2007) Tetravalent dengue specific domain III based chimeric recombinant protein. WO 2007034507
5. Batra G, Raut R, Dahiya S, Kamran N, Swaminathan S, Khanna N (2010a) Pichia pastoris-expressed dengue virus type 2 envelope domain III elicits virus-neutralizing antibodies. J Virol Methods 167:10–16. doi:10.1016/j.jviromet.2010.03.002
6. Batra G, Talha SM, Nemani SK, Dhar N, Swaminathan S, Khanna N (2010b) Expression, purification and characterization of in vivo biotinylated dengue virus envelope domain III based tetravalent antigen. Protein Expr Purif 74:99–105. doi:10.1016/j.pep.2010.04.017
7. Bellucci M, De Marchis F, Ferradini N, Pompa A, Veronesi F, Rosellini D (2015) A mutant Synechococcus gene encoding glutamate 1-semialdehyde aminotransferase confers gabaculine resistance when expressed in tobacco plastids. Plant Cell Rep 34(12):2127–2136. doi:10.1007/s00299-015-1856-z
8. Bendich AJ (1987) Why do chloroplasts and mitochondria contain so many copies of their genome? BioEssays 6:279–282. doi:10.1002/bies.950060608
9. Birch-Machin I, Newell CA, Hibberd JM, Gray JC (2004) Accumulation of rotavirus VP6 protein in chloroplasts of transplastomic tobacco is limited by protein stability. Plant Biotechnol J 2:261–270. doi:10.1111/j.1467-7652.2004.00072.x
10. Bock R (2014) Genetic engineering of the chloroplast: novel tools and new applications. Curr Opin Biotechnol 26:7–13. doi:10.1016/j.copbio.2013.06.004
11. Bock R (2015) Engineering plastid genomes: methods, tools, and applications in basic research and biotechnology. Annu Rev Plant Biol 66:3.1–3.31
12. Bock R, Warzecha H (2010) Solar-powered factories for new vaccines and antibiotics. Trends Biotechnol 28:246–252. doi:10.1016/j.tibtech.2010.01.006
13. Buhot L, Horvath E, Medgyesy P, Lerbs-Mache S (2006) Hybrid transcription system for controlled plastid transgene expression. Plant J 46:700–707. doi:10.1111/j.1365-313X.2006.02718.x
14. Buntru M, Gartner S, Staib L, Kreuzaler F, Schlaich N (2013) Delivery of multiple transgenes to plant cells by an improved version of Multiround Gateway technology. Transgenic Res 22:153–167. doi:10.1007/s11248-012-9640-0
15. Caddick MX et al (1998) An ethanol inducible gene switch for plants used to manipulate carbon metabolism. Nat Biotechnol 16:177–180. doi:10.1038/nbt0298-177
16. Cahoon EB, Shanklin J, Ohlrogge JB (1992) Expression of a coriander desaturase results in petroselinic acid production in transgenic tobacco. Proc Natl Acad Sci USA 89:11184–11188
17. Capeding MR et al (2014) Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet 384:1358–1365. doi:10.1016/s0140-6736(14)61060-6
18. Cardoso SA, Paixao VF, Oliveira MD, Honda ER, Oliveira LL, da Silva CC, De Paula SO (2013) Dengue-1 envelope protein domain III produced in Pichia pastoris: potential use for serological diagnosis. Protein Expr Purif 92:9–13. doi:10.1016/j.pep.2013.08.014
19. Chaturvedi UC, Nagar R (2008) Dengue and dengue haemorrhagic fever: Indian perspective. J Biosci 33:429–441
20. Clarke J, Daniell H (2011) Plastid biotechnology for crop production: present status and future perspectives. Plant Mol Biol 76:211–220. doi:10.1007/s11103-011-9767-z
21. Clarke JL, Zhang P (2013) Plant biotechnology for food security and bioeconomy. Plant Mol Biol 83:1–3. doi:10.1007/s11103-013-0097-1
22. Clements DE et al (2010) Development of a recombinant tetravalent dengue virus vaccine: immunogenicity and efficacy studies in mice and monkeys. Vaccine 28:2705–2715. doi:10.1016/j.vaccine.2010.01.022
23. Daniell H (1997) Transformation and foreign gene expression in plants mediated by microprojectile bombardment. In: Tuan RS (ed) Recombinant gene expression protocols. Methods in molecular biology, vol 62. Humana Press Inc, NJ, pp 463–489. doi:10.1385/0-89603-480-1:463
24. Daniell H (2006) Henry Daniell: chloroplast genetic engineering. Biotechnol J 1:31–33. doi:10.1002/biot.200690011
25. Dasgupta S, Collins GB, Hunt AG (1998) Co-ordinated expression of multiple enzymes in different subcellular compartments in plants. Plant J 16:107–116. doi:10.1046/j.1365-313x.1998.00255.x
26. De Marchis F, Pompa A, Bellucci M (2012) Plastid proteostasis and heterologous protein accumulation in transplastomic plants. Plant Physiol 160:571–581. doi:10.1104/pp.112.203778
27. De Marchis F, Bellucci M, Pompa A (2016) Phaseolin expression in tobacco chloroplast reveals an autoregulatory mechanism in heterologous protein translation. Plant Biotechnol J 14(2):603–614. doi:10.1111/pbi.12405
28. Dubin M, Bowler C, Benvenuto G (2008) A modified Gateway cloning strategy for overexpressing tagged proteins in plants. Plant Methods 4:1746–4811
29. Dubin MJ, Bowler C, Benvenuto G (2010) Overexpressing tagged proteins in plants using a modified gateway cloning strategy. Cold Spring Harbor Protoc. doi:10.1101/pdb.prot5401
30. Earley KW, Haag JR, Pontes O, Opper K, Juehne T, Song K, Pikaard CS (2006) Gateway-compatible vectors for plant functional genomics and proteomics. Plant J 45:616–629. doi:10.1111/j.1365-313X.2005.02617.x
31. Eberhard S, Drapier D, Wollman FA (2002) Searching limiting steps in the expression of chloroplast-encoded proteins: relations between gene copy number, transcription, transcript abundance and translation rate in the chloroplast of Chlamydomonas reinhardtii. Plant J 31:149–160
32. Emadpour M, Karcher D, Bock R (2015) Boosting riboswitch efficiency by RNA amplification. Nucleic Acids Res 43:e66. doi:10.1093/nar/gkv165
33. Etemad B, Batra G, Raut R, Dahiya S, Khanam S, Swaminathan S, Khanna N (2008) An envelope domain III-based chimeric antigen produced in Pichia pastoris elicits neutralizing antibodies against all four dengue virus serotypes. Am J Trop Med Hyg 79:353–363
34. Fischer R, Schillberg S, Hellwig S, Twyman RM, Drossard J (2012) GMP issues for recombinant plant-derived pharmaceutical proteins. Biotechnol Adv 30:434–439. doi:10.1016/j.biotechadv.2011.08.007
35. Fischer R, Schillberg S, Buyel JF, Twyman RM (2013) Commercial aspects of pharmaceutical protein production in plants. Curr Pharm Des 19:5471–5477
36. Fischer R, Vasilev N, Twyman RM, Schillberg S (2015) High-value products from plants: the challenges of process optimization. Curr Opin Biotechnol 32:156–162. doi:10.1016/j.copbio.2014.12.018
37. Ghosh A, Dar L (2015) Dengue vaccines: challenges, development, current status and prospects Indian. J Med Microbiol 33:3–15
38. Gottschamel J, Waheed MT, Clarke JL, Lossl AG (2013) A novel chloroplast transformation vector compatible with the Gateway((R)) recombination cloning technology. Transgenic Res 22:1273–1278. doi:10.1007/s11248-013-9726-3
39. Gubler DJ (2012) The economic burden of dengue. Am J Trop Med Hyg 86(5):743–744. doi:10.4269/ajtmh.2012.12-0157
40. Guirakhoo F et al (2001) Construction, safety, and immunogenicity in nonhuman primates of a chimeric yellow fever-dengue virus tetravalent vaccine. J Virol 75:7290–7304. doi:10.1128/jvi.75.16.7290-7304.2001
41. Guy B, Barrere B, Malinowski C, Saville M, Teyssou R, Lang J (2011) From research to phase III: preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccine. Vaccine 29:7229–7241. doi:10.1016/j.vaccine.2011.06.094
42. Guzman MG, Hermida L, Bernardo L, Ramirez R, Guillen G (2010) Domain III of the envelope protein as a dengue vaccine target. Expert Rev Vaccines 9:137–147. doi:10.1586/erv.09.139
43. Hadinegoro SR et al (2015) Efficacy and long-term safety of a dengue vaccine in regions of endemic disease. N Engl J Med. doi:10.1056/NEJMoa1506223
44. Hennig A, Bonfig K, Roitsch T, Warzecha H (2007) Expression of the recombinant bacterial outer surface protein A in tobacco chloroplasts leads to thylakoid localization and loss of photosynthesis. Febs J 274:5749–5758. doi:10.1111/j.1742-4658.2007.06095.x
45. Herz S, Füßl M, Steiger S, Koop H-U (2005) Development of novel types of plastid transformation vectors and evaluation of factors controlling expression. Transgenic Res 14:969–982. doi:10.1007/s11248-005-2542-7
46. Hombach J et al (2005) Review on flavivirus vaccine development. In: Proceedings of a meeting jointly organised by the World Health Organization and the Thai Ministry of Public Health, 26–27 April 2004, Bangkok, Thailand. Vaccine 23:2689–2695
47. Ivy J, Nakano E, Clements D (2000) Subunit immunogenic composition against dengue infection
48. Jaiswal S, Khanna N, Swaminathan S (2004) High-level expression and one-step purification of recombinant dengue virus type 2 envelope domain III protein in Escherichia coli. Protein Expr Purif 33:80–91. doi:10.1016/j.pep.2003.09.009
49. Kahlau S, Bock R (2008) Plastid transcriptomics and translatomics of tomato fruit development and chloroplast-to-chromoplast differentiation: chromoplast gene expression largely serves the production of a single protein. Plant Cell 20:856–874. doi:10.1105/tpc.107.055202
50. Kanagaraj AP, Verma D, Daniell H (2011) Expression of dengue-3 premembrane and envelope polyprotein in lettuce chloroplasts. Plant Mol Biol 76:323–333. doi:10.1007/s11103-011-9766-0
51. Karimi M, Inzé D, Depicker A (2002) GATEWAY™ vectors for Agrobacterium-mediated planttransformation. Trends Plant Sci 7:193–195
52. Karimi M, Depicker A, Hilson P (2007) Recombinational cloning with plant gateway vectors. Plant Physiol 145:1144–1154
53. Karimi M, Inze D, Van Lijsebettens M, Hilson P (2013) Gateway vectors for transformation of cereals. Trends Plant Sci 18:1–4. doi:10.1016/j.tplants.2012.10.001
54. ® recombinational cloning: a biological operating system. Expert Opin Drug Discov 2:571–589. doi:10.1517/17460441.2.4.571
55. Khanam S, Etemad B, Khanna N, Swaminathan S (2006) Induction of neutralizing antibodies specific to dengue virus serotypes 2 and 4 by bivalent antigen composed of linked envelop domains III of these two serotypes. Am J Trop Med Hyg 74:266–277
56. Kim J, Klein PG, Mullet JE (1994) Synthesis and turnover of photosystem II reaction center protein D1. Ribosome pausing increases during chloroplast development. J Biol Chem 269:17918–17923
57. Kim TG, Kim MY, Huy NX, Kim SH, Yang MS (2013) M cell-targeting ligand and consensus dengue virus envelope protein domain III fusion protein production in transgenic rice calli. Mol Biotechnol 54(3):880–887. doi:10.1007/s12033-012-9637-1
58. Koop H-U, Herz S, Golds T, Nickelsen J (2007) The genetic transformation of plastids. In: Bock R (ed) Cell and molecular biology of plastids, vol 19. Topics in current genetics. Springer, Heidelberg, pp 457–510. doi:10.1007/4735_2007_0225
59. Kuhn RJ et al (2002) Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108:717–725
60. Kuroda H, Maliga P (2001) Complementarity of the 16S rRNA penultimate stem with sequences downstream of the AUG destabilizes the plastid mRNAs. Nucleic Acids Res 29:970–975
61. Lössl AG, Waheed MT (2011) Chloroplast-derived vaccines against human diseases: achievements, challenges and scopes. Plant Biotechnol J 9:527–539. doi:10.1111/j.1467-7652.2011.00615.x
62. Lössl A, Eibl C, Harloff HJ, Jung C, Koop HU (2003) Polyester synthesis in transplastomic tobacco (Nicotiana tabacum L.): significant contents of polyhydroxybutyrate are associated with growth reduction. Plant Cell Rep 21:891–899. doi:10.1007/s00299-003-0610-0
63. Lössl A, Bohmert K, Harloff H, Eibl C, Mühlbauer S, Koop H-U (2005) Inducible trans-activation of plastid transgenes: expression of the R. eutropha phb operon in transplastomic tobacco. Plant Cell Physiol 46:1462–1471
64. Lu Y, Rijzaani H, Karcher D, Ruf S, Bock R (2013) Efficient metabolic pathway engineering in transgenic tobacco and tomato plastids with synthetic multigene operons. Proc Natl Acad Sci USA 110:E623–E632. doi:10.1073/pnas.1216898110
65. Lyska D, Engelmann K, Meierhoff K, Westhoff P (2013) pAUL: a gateway-based vector system for adaptive expression and flexible tagging of proteins in Arabidopsis. PLoS ONE. doi:10.1371/journal.pone.0053787
66. Ma S, Wang A (2012) Molecular farming: an Overview. In: Wang A, Ma S (eds) Molecular farming in plants: recent advances and future prospects. Springer, Netherlands, pp 1–20
67. Magee AM, Coyne S, Murphy D, Horvath EM, Medgyesy P, Kavanagh TA (2004) T7 RNA polymerase-directed expression of an antibody fragment transgene in plastids causes a semi-lethal pale-green seedling phenotype. Transgenic Res 13:325–337
68. Maliga P, Bock R (2011) Plastid biotechnology: food, fuel, and medicine for the 21st century. Plant Physiol 155:1501–1510
69. Martinez CA, Topal E, Giulietti AM, Talou JR, Mason H (2010) Exploring different strategies to express dengue virus envelope protein in a plant system. Biotechnol Lett 32:867–875. doi:10.1007/s10529-010-0236-6
70. McBride KE, Schaaf DJ, Daley M, Stalker DM (1994) Controlled expression of plastid transgenes in plants based on a nuclear DNA-encoded and plastid-targeted T7 RNA polymerase. Proc Natl Acad Sci USA 91:7301–7305
71. McDonald W, Powell T, Price A, Becker R (2009) Compositions of dengue viral proteins and methods of use
72. Melnik S, Stöger E (2013) Green factories for biopharmaceuticals. Curr Med Chem 20:1038–1046
73. Modis Y, Ogata S, Clements D, Harrison SC (2003) A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci 100:6986–6991
74. Modis Y, Ogata S, Clements D, Harrison SC (2004) Structure of the dengue virus envelope protein after membrane fusion. Nature 427:313–319. doi:10.1038/nature02165
75. Mühlbauer SK, Koop H-U (2005) External control of transgene expression in tobacco plastids using the bacterial lac repressor. Plant J 43:941–946. doi:10.1111/j.1365-313X.2005.02495.x
76. Mukhopadhyay S, Kuhn RJ, Rossmann MG (2005) A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 3:13–22. doi:10.1038/nrmicro1067
77. Murashige T, Skoog F (1962) A revised medium for rapid growth and bio-assays with tobacco tissue cultures. Physiol Plant 15(3):473–497
78. Murray M, Thompson W (1980) Rapid isolation of high molecular weight plant DNA. Nucleic Acids Res 8:4321–4326. doi:10.1093/nar/8.19.4321
79. Nakakura M, Hibi Y, Okamoto T, Sugiura M (2016) Cooperation between the chloroplast psbA 5′-untranslated region and coding region is important for translational initiation: the chloroplast translation machinery cannot read a human viral gene coding region. The Plant J 85:772–780. doi:10.1111/tpj.13150
80. Nawrath C, Poirier Y, Somerville C (1994) Targeting of the polyhydroxybutyrate biosynthetic pathway to the plastids of Arabidopsis thaliana results in high levels of polymer accumulation. Proc Natl Acad Sci 91:12760–12764
81. New JS, Westerveld D, Daniell H (2012) Chloroplast-derived therapeutic and prophylactic vaccines. In: Wang A, Ma S (eds) Molecular farming in plants: recent advances and future prospects. Springer, Netherlands, pp 69–87
82. Nguyen NL, So KK, Kim JM, Kim SH, Jang YS, Yang MS, Kim DH (2015) Expression and characterization of an M cell-specific ligand-fused dengue virus tetravalent epitope using Saccharomyces cerevisiae. J Biosci Bioeng 119:19–27
83. Oey M, Lohse M, Kreikemeyer B, Bock R (2009a) Exhaustion of the chloroplast protein synthesis capacity by massive expression of a highly stable protein antibiotic. Plant J 57:436–445. doi:10.1111/j.1365-313X.2008.03702.x
84. Oey M, Lohse M, Scharff LB, Kreikemeyer B, Bock R (2009b) Plastid production of protein antibiotics against pneumonia via a new strategy for high-level expression of antimicrobial proteins. Proc Natl Acad Sci USA 106:6579–6584. doi:10.1073/pnas.0813146106
85. Petersen K, Bock R (2011) High-level expression of a suite of thermostable cell wall-degrading enzymes from the chloroplast genome. Plant Mol Biol 76:311–321. doi:10.1007/s11103-011-9742-8
86. Rappsilber J, Ishihama Y, Mann M (2003) Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal Chem 75:663–670
87. Roslan HA et al (2001) Characterization of the ethanol-inducible alc gene-expression system in Arabidopsis thaliana. Plant J 28:225–235. doi:10.1046/j.1365-313X.2001.01146.x
88. Ruf S, Hermann M, Berger IJ, Carrer H, Bock R (2001) Stable genetic transformation of tomato plastids and expression of a foreign protein in fruit. Nat Biotechnol 19:870–875. doi:10.1038/nbt0901-870
89. Ruf S, Karcher D, Bock R (2007) Determining the transgene containment level provided by chloroplast transformation. Proc Natl Acad Sci USA 104:6998–7002. doi:10.1073/pnas.0700008104
90. Saejung W et al (2007) Production of dengue 2 envelope domain III in plant using TMV-based vector system. Vaccine 25:6646–6654. doi:10.1016/j.vaccine.2007.06.029
91. Salter MG, Paine JA, Riddell KV, Jepson I, Greenland AJ, Caddick MX, Tomsett AB (1998) Characterisation of the ethanol-inducible-alc-gene expression system for transgenic plants. Plant J 16:127–132. doi:10.1046/j.1365-313x.1998.00281.x
92. Scotti N, Cardi T (2014) Transgene-induced pleiotropic effects in transplastomic plants. Biotechnol Lett 36:229–239. doi:10.1007/s10529-013-1356-6
93. Scotti N, Bellucci M, Cardi T (2013) The chloroplasts as platform for recombinant proteins production. In: Translation in mitochondria and other organelles. Springer, Heidelberg, pp 225–262. doi:10.1007/978-3-642-39426-3_10
94. Scotti N et al (2015) The HIV-1 Pr55gag polyprotein binds to plastidial membranes and leads to severe impairment of chloroplast biogenesis and seedling lethality in transplastomic tobacco plants. Transgenic Res 24:319–331. doi:10.1007/s11248-014-9845-5
95. Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M (2006) In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc 1:2856–2860. doi:10.1038/nprot.2006.468
96. Simmons M, Hayes C, Porter K (1999) Recombinant dengue virus envelop protein/maltose-binding protein antigens and subunit vaccine compositions containing said antigens
97. Srivastava A, Putnak J, Hoke C, Warren R (2000) Recombinant vaccine made in E.coli against dengue virus
98. Staub JM, Maliga P (1993) Accumulation of D1 polypeptide in tobacco plastids is regulated via the untranslated region of the psbA mRNA. EMBO J 12(2):601–606
99. Svab Z, Maliga P (1993) High-frequency plastid transformation in tobacco by selection for a chimeric aadA gene. Proc Natl Acad Sci USA 90:913–917
100. Svab Z, Maliga P (2007) Exceptional transmission of plastids and mitochondria from the transplastomic pollen parent and its impact on transgene containment. Proc Natl Acad Sci USA 104:7003–7008. doi:10.1073/pnas.0700063104
101. Tabor S, Richardson CC (1985) A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes. Proc Natl Acad Sci 82:1074–1078
102. Thomas SJ (2015) Preventing dengue–is the possibility now a reality? N Engl J Med 372:172–173. doi:10.1056/NEJMe1413146
103. Tissot G, Canard H, Nadai M, Martone A, Botterman J, Dubald M (2008) Translocation of aprotinin, a therapeutic protease inhibitor, into the thylakoid lumen of genetically engineered tobacco chloroplasts. Plant Biotechnol J 6:309–320. doi:10.1111/j.1467-7652.2008.00321.x
104. Tregoning JS et al (2003) Expression of tetanus toxin fragment C in tobacco chloroplasts. Nucleic Acids Res 31:1174–1179
105. Tripathi NK, Babu JP, Shrivastva A, Parida M, Jana AM, Rao PV (2008) Production and characterization of recombinant dengue virus type 4 envelope domain III protein. J Biotechnol 134:278–286. doi:10.1016/j.jbiotec.2008.02.001
106. Tripathi NK, Shrivastava A, Biswal KC, Rao PV (2011) Recombinant dengue virus type 3 envelope domain III protein from Escherichia coli. Biotechnol J 6:604–608. doi:10.1002/biot.201000399
107. Tungsuchat T, Kuroda H, Narangajavana J, Maliga P (2006) Gene activation in plastids by the CRE site-specific recombinase. Plant Mol Biol 61:711–718. doi:10.1007/s11103-006-0044-5
108. Tuse D, Tu T, McDonald KA (2014) Manufacturing economics of plant-made biologics: case studies in therapeutic and industrial enzymes. Biomed Res Int 2014:256135. doi:10.1155/2014/256135
109. Verhounig A, Karcher D, Bock R (2010) Inducible gene expression from the plastid genome by a synthetic riboswitch. Proc Natl Acad Sci 107:6204–6209
110. Villar L et al (2015) Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med 372(2):113–123. doi:10.1056/NEJMoa1411037
111. Waheed MT et al (2011) Plastid expression of a double-pentameric vaccine candidate containing human papillomavirus-16 L1 antigen fused with LTB as adjuvant: transplastomic plants show pleiotropic phenotypes. Plant Biotechnol J 9:651–660. doi:10.1111/j.1467-7652.2011.00612.x
112. Wani S, Sah S, Sági L, Solymosi K (2015) Transplastomic plants for innovations in agriculture. A review agronomy for sustainable development:1–40 doi:10.1007/s13593-015-0310-5
113. Weaver SC, Vasilakis N (2009) Molecular evolution of dengue viruses: contributions of phylogenetics to understanding the history and epidemiology of the preeminent arboviral disease infection. Genet Evolut 9:523–540. doi:10.1016/j.meegid.2009.02.003
114. WHO (2015) Factsheet on dengue and dengue haemorrhagic fever. World Health Organization. http://www.who.int/mediacentre/factsheets/fs117/en/
115. Ye GN, Hajdukiewicz PTJ, Broyles D, Rodriguez D, Xu CW, Nehra N, Staub JM (2001) Plastid-expressed 5-enolpyruvylshikimate-3-phosphate synthase genes provide high level glyphosate tolerance in tobacco. Plant J 25:261–270. doi:10.1046/j.1365-313x.2001.00958.x
116. Yusibov V, Streatfield SJ, Kushnir N (2011) Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond. Hum Vaccinces 7:313–321
117. Zhao H et al (2014) Induction of neutralizing antibodies against four serotypes of dengue viruses by MixBiEDIII, a tetravalent dengue vaccine. PLoS ONE 9:e86573. doi:10.1371/journal.pone.0086573
118. Zhou F et al (2008) High-level expression of human immunodeficiency virus antigens from the tobacco and tomato plastid genomes. Plant Biotechnol J 6:897–913. doi:10.1111/j.1467-7652.2008.00356.x