1921
Volume 79, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

There is currently no vaccine to prevent dengue (DEN) virus infection, which is caused by any one of four closely related serotypes, DEN-1, DEN-2, DEN-3, or DEN-4. A DEN vaccine must be tetravalent, because immunity to a single serotype does not offer cross-protection against the other serotypes. We have developed a novel tetravalent chimeric protein by fusing the receptor-binding envelope domain III (EDIII) of the four DEN virus serotypes. This protein was expressed in the yeast, and purified to near homogeneity in high yields. Antibodies induced in mice by the tetravalent protein, formulated in different adjuvants, neutralized the infectivity of all four serotypes. This, coupled with the high expression potential of the system and easy one-step purification, makes the EDIII-based recombinant protein a potentially promising candidate for the development of a safe, efficacious, and inexpensive, tetravalent DEN vaccine.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2008.79.353
2008-09-01
2017-11-20
Loading full text...

Full text loading...

/deliver/fulltext/14761645/79/3/0790353.html?itemId=/content/journals/10.4269/ajtmh.2008.79.353&mimeType=html&fmt=ahah

References

  1. Lindenbach BD, Rice CM, 2001. Flaviviridae: the viruses and their replication. Knipe DM, Howley PM, eds. Field’s Virology. Fourth edition. Philadelphia, PA: Lippincott Williams & Wilkins, 991–1041.
  2. Gubler DJ, 1998. Dengue and dengue haemorrhagic fever. Clin Microbiol Rev 11 : 480–496.
  3. Guzmán MG, Kouri G, 2002. Dengue: an update. Lancet Infect Dis 2 : 33–42.
  4. Gibbons RV, Vaughn DW, 2002. Dengue: an escalating problem. BMJ 324 : 1563–1566.
  5. Innis BL, 1997. Antibody responses to dengue virus infection. Gubler DJ, Kuno G, eds. Dengue and Dengue Hemorrhagic Fever. New York: CAB International, 221–243.
  6. Halstead SB, Heinz FX, Barrett ADT, Roehrig JT, 2005. Conference report on Dengue virus: molecular basis of cell entry and pathogenesis, 25–27 June 2003, Vienna, Austria. Vaccine 23 : 849–856.
  7. Kurane I, Ennis FA, 1997. Immunopathogenesis of dengue virus infections. Gubler DJ, Kuno G, eds. Dengue and Dengue Hemorrhagic Fever. Wallingford: CAB International, 273–290.
  8. Hombach J, Barrett AD, Cardosa MJ, Deubel V, Guzman M, Kurane I, Roehrig JT, Sabchareon A, Kieny MP, 2005. Meeting report on Review on flavivirus vaccine development: proceedings of a meeting jointly organized by the World Health Organization and the Thai ministry of public health, 26–27 April 2004, Bangkok, Thailand. Vaccine 23 : 2689–2695.
  9. Kanesa-thasan N, Sun W, Kim-Ahn G, Van Albert S, Putnak JR, King A, Raengsakulsrach B, Christ-Schmidt H, Gilson K, Zahradnik JM, Vaughn DW, Innis BL, Saluzzo JF, Hoke CHJr, 2001. Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers. Vaccine 19 : 3179–3188.
  10. Edelman R, Wasserman SS, Bodison SA, Putnak RJ, Eckels KH, Tang D, Kanesa-Thasan N, Vaughn DW, Innis BL, Sun W, 2003. Phase I trial of 16 formulations of a tetravalent live-attenuated dengue vaccine. Am J Trop Med Hyg 69 (Suppl 6): 48–60.
  11. Kitchener S, Nissen M, Nasveld P, Forrat R, Yoksan S, Lang J, Saluzzo JF, 2006. Immunogenicity and safety of two live-attenuated tetravalent dengue vaccine formulations in healthy Australian adults. Vaccine 24 : 1238–1241.
  12. Guirakhoo F, Arroyo J, Pugachev KV, Miller C, Zhang ZX, Weltzin R, Georgakopoulos K, Catalan J, Ocran S, Soike K, Ratterree M, Monath TP, 2001. Construction, safety, and im-munogenicity in nonhuman primates of a chimeric yellow fever-dengue virus tetravalent vaccine. J Virol 75 : 7290–7304.
  13. Guirakhoo F, Kitchener S, Morrison D, Forrat R, McCarthy K, Nichols R, Yoksan S, Duan X, Ermak TH, Kanesa-Thasan N, Bedford P, Lang J, Quentin-Millet MJ, Monath TP, 2006. Live attenuated chimeric yellow fever dengue type 2 (Chi-meriVaxTM-DEN2) vaccine: phase I clinical trial for safety and immunogenicity: effect of yellow fever prior immunity in induction of cross neutralizing antibody responses to all. Human Vaccines 2 : 60–67.
  14. Seligman SJ, Gould EA, 2004. Live flavivirus vaccines: reasons for caution. Lancet 363 : 2073–2075.
  15. Putnak R, Feighny R, Burrous J, Cochran M, Hackett C, Smith G, Hoke C, 1991. Dengue-1 virus envelope glycoprotein gene expressed in recombinant baculovirus elicits virus-neutralizing antibody in mice and protects them from virus challenge. Am J Trop Med Hyg 45 : 159–167.
  16. Delenda C, Staropoli I, Frenkiel MP, Cabanié L, Deubel V, 1994. Analysis of C-terminally truncated dengue 2 and dengue 3 virus envelope glycoproteins: processing in insect cells and im-munogenic properties in mice. J Gen Virol 75 : 1569–1578.
  17. Simmons M, Nelson WM, Wu SJ, Hayes CG, 1998. Evaluation of the protective efficacy of a recombinant dengue envelope B domain fusion protein against dengue 2 virus infection in mice. Am J Trop Med Hyg 58 : 655–662.
  18. Kelly EP, Greene JJ, King AD, Innis BL, 2000. Purified dengue 2 virus envelope glycoprotein aggregates produced by bacu-lovirus are immunogenic in mice. Vaccine 18 : 2549–2559.
  19. Konishi E, Yamaoka M, Kurane I, Mason PW, 2000. A DNA vaccine expressing dengue type 2 virus premembrane and envelope genes induces neutralizing antibody and memory B cells in mice. Vaccine 18 : 1133–1139.
  20. Men R, Wyatt L, Tokimatsu I, Arakaki S, Shameem G, Elkins R, Chanock R, Moss B, Lai CJ, 2000. Immunization of rhesus monkeys with a recombinant of modified vaccinia virus An-kara expressing a truncated envelope glycoprotein of dengue type 2 virus induced resistance to dengue type 2 virus challenge. Vaccine 18 : 3113–3122.
  21. Simmons M, Murphy GS, Hayes CG, 2001. Short report: antibody responses of mice immunized with a tetravalent dengue recombinant protein subunit vaccine. Am J Trop Med Hyg 65 : 159–161.
  22. Hermida L, Rodríguez R, Lazo L, Lopez C, Márquez G, Páez R, Suárez C, Espinosa R, Garcia J, Guzmán G, Guillén G, 2002. A recombinant envelope protein from dengue virus purified by IMAC is bioequivalent with its immune-affinity chromatography purified counterpart. J Biotechnol 94 : 213–216.
  23. Muné M, Rodríguez R, Ramírez R, Soto Y, Sierra B, Roche RR, Marquez G, Garcia J, Guillén G, Guzmán MG, 2003. Carboxy-terminally truncated dengue 4 virus envelope glycoprotein expressed in Pichia pastoris induced neutralizing antibodies and resistance to dengue 4 virus challenge in mice. Arch Virol 148 : 2267–2273.
  24. Wei HY, Jiang LF, Xue YH, Fang DY, Guo HY, 2003. Secreted expression of dengue virus type 2 full-length envelope glyco-protein in Pichia pastoris. J Virol Methods 109 : 17–23.
  25. Hermida L, Rodríguez R, Lazo L, Bernardo L, Silva R, Zulueta A, López C, Martín J, Valdes I, del Rosario D, Guillén G, Guzmán MG, 2004. A fragment of the envelope protein from dengue-1 virus, fused in two different sites of the meningococ-cal P64k protein carrier, induces a functional immune response in mice. Biotechnol Appl Biochem 39 : 107–114.
  26. Hermida L, Rodríguez R, Lazo L, Silva R, Zulueta A, Chinea G, López C, Guzmán MG, Guillén G, 2004. A dengue-2 envelope fragment inserted within the structure of the P64k meningo-coccal protein carrier enables a functional immune response against the virus in mice. J Virol Methods 115 : 41–49.
  27. Mota J, Acosta M, Argotte R, Figueroa R, Méndez A, Ramos C, 2005. Induction of protective antibodies against dengue virus by tetravalent DNA immunization of mice with domain III of the envelope protein. Vaccine 23 : 3469–3476.
  28. Apt D, Raviprakash K, Brinkman A, Semyonov A, Yang S, Skinner C, Diehl L, Lyons R, Porter K, Punnonen J, 2006. Tetravalent neutralizing antibody response against four dengue sero-types by a single chimeric dengue envelope antigen. Vaccine 24 : 335–344.
  29. Konishi E, Kosugi S, Imoto JI, 2006. Dengue tetravalent DNA vaccine inducing neutralizing antibody and anamnestic responses to four serotypes in mice. Vaccine 24 : 2200–2207.
  30. Hermida L, Bernardo L, Martín J, Alvarez M, Prado I, López C, Sierra B, Martínez R, Rodríguez R, Zulueta A, Pérez AB, Lazo L, Rosario D, Guillén G, Guzmán MG, 2006. A recombinant fusion protein containing the domain III of the dengue-2 envelope protein is immunogenic and protective in non-human primates. Vaccine 24 : 3165–3171.
  31. Zulueta A, Martín J, Hermida L, Alvarez M, Valdés I, Prado I, Chinea G, Rosario D, Guillén G, Guzmán MG, 2006. Amino acid changes in the recombinant dengue 3 envelope domain III determine its antigenicity and immunogenicity in mice. Virus Res 121 : 65–73.
  32. Raja NU, Holman DH, Wang D, Raviprakash K, Juompan LY, Deitz SB, Luo M, Zhang J, Porter KR, Dong JY, 2007. Induction of bivalent immune responses by expression of dengue virus type 1 and type 2 antigens from a single complex aden-oviral vector. Am J Trop Med Hyg 76 : 743–751.
  33. Holman DH, Wang D, Raviprakash K, Raja NU, Luo M, Zhang J, Porter KR, Dong JY, 2007. Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes. Clin Vac Immunol 14 : 182–189.
  34. Khanam S, Etemad B, Khanna N, Swaminathan S, 2006. Induction of neutralizing antibodies specific to dengue virus sero-types 2 and 4 by a bivalent antigen composed of linked envelope domains III of these two serotypes. Am J Trop Med Hyg 74 : 266–277.
  35. Khanam S, Khanna N, Swaminathan S, 2006. Induction of antibodies and T cell responses by dengue virus type 2 envelope domain III encoded by plasmid and adenoviral vectors. Vaccine 24 : 6513–6525.
  36. Khanam S, Rajendra P, Khanna N, Swaminathan S, 2007. An adenovirus prime/plasmid boost strategy for induction of equi-potent immune responses to two dengue virus serotypes. BMC Biotechnol 7 : 10.
  37. Modis Y, Ogata S, Clements D, Harrison SC, 2003. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci USA 100 : 6986–6991.
  38. Modis Y, Ogata S, Clements D, Harrison SC, 2005. Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein. J Virol 79 : 1223–1231.
  39. Chen Y, Maguire T, Hileman RE, Fromm JR, Esko JD, Linhardt RJ, Marks RM, 1997. Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat Med 3 : 866–871.
  40. Mégret F, Hugnot JP, Falconar A, Gentry MK, Morens DM, Murray JM, Schlesinger JJ, Wright PJ, Young P, van Regen-mortel MHV, Deubel V, 1992. Use of recombinant fusion proteins and monoclonal antibodies to define linear and discontinuous antigenic sites on the dengue envelope glycoprotein. Virology 187 : 480–491.
  41. Roehrig JT, Johnson AJ, Hunt AR, Bolin RA, Chu MC, 1990. Antibodies to dengue 2 virus E-glycoprotein synthetic peptides identify antigenic conformation. Virology 177 : 668–675.
  42. Roehrig JT, Bolin RA, Kelly RG, 1998. Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica. Virology 246 : 317–328.
  43. Churdboonchart V, Bhamarapravati N, Peampramprecha S, Siri-navin S, 1991. Antibodies against dengue viral proteins in primary and secondary dengue hemorrhagic fever. Am J Trop Med Hyg 44 : 481–493.
  44. Crill WD, Roehrig RT, 2001. Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. J Virol 75 : 7769–7773.
  45. Bhardwaj S, Holbrook M, Shope RE, Barrett ADT, Watowich SJ, 2001. Biophysical characterization and vector-specific antagonist activity of domain III of the tick-borne flavivirus envelope protein. J Virol 75 : 4002–4007.
  46. Hung JJ, Hsieh MT, Young MJ, Kao CL, King CC, Chang W, 2004. An external loop region of domain III of dengue virus type 2 envelope protein is involved in serotype-specific binding to mosquito but not mammalian cells. J Virol 78 : 378–388.
  47. Chin JFL, Chu JJH, Ng ML, 2007. The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit virus entry. Microbes Infect 9 : 1–6.
  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 Exp Purif 33 : 80–91.
  49. Roehrig JT, Volpe KE, Squires J, Hunt AR, Davis BS, Chang GJ, 2004. Contribution of disulfide bridging to epitope expression of the dengue type 2 virus envelope glycoprotein. J Virol 78 : 2648–2652.
  50. Kuhn RJ, Zhang W, Rossman MG, Pletnev SV, Corver J, Lenches E, Jones CT, Mukhopadhyay S, Chipman PR, Strauss EG, Baker TS, Strauss JH, 2002. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108 : 717–725.
  51. Wang S, He R, Anderson R, 1999. PrM- and cell-binding domains of the dengue virus E protein. J Virol 73 : 2547–2551.
  52. Cereghino GP, Lin Cereghino J, Ilgen C, Cregg JM, 2002. Production of recombinant proteins in fermenter cultures of the yeast Pichia pastoris. Curr Opin Biotechnol 13 : 329–332.
  53. Macauley-Patrick S, Fazenda ML, McNeil B, Harvey LM, 2005. Heterologous protein production using the Pichia pastoris expression system. Yeast 22 : 249–270.
  54. Cregg JM, Tschopp JF, Stillman C, Siegel R, Akong M, Craig WS, Buckholz RG, Madden KR, Kellaris PA, Davis GR, Smi-ley BL, Cruze J, Torregrossa R, Velicelibi G, Thill GP, 1987. High level expression and efficient assembly of hepatitis B surface antigen in the methylotrophic yeast, Pichia pastoris. Biotechnology (NY) 5 : 479–485.
  55. Vassileva A, Chugh DA, Swaminathan S, Khanna N, 2001. Effect of copy number on the expression levels of hepatitis B surface antigen in the methylotrophic yeast Pichia pastoris. Protein Exp Purif 21 : 71–80.
  56. Kjeldsen T, Pettersson AF, Hach M, 1999. Secretory expression and characterization of insulin in Pichia pastoris. Biotechnol Appl Biochem 29 : 79–86.
  57. Russell PK, Nisalak A, Sukhavachana P, Vivona S, 1967. A plaque reduction test for dengue virus neutralizing antibodies. J Immunol 99 : 285–290.
  58. Durbin AP, Karron RA, Sun W, Vaughn DW, Reynolds MJ, Perreault JP, Thumar B, Men R, Lai CJ, Elkins WR, Chanock RM, Murphy BR, Whitehead SS, 2001. Attenuation and im-munogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3′-untranslated region. Am J Trop Med Hyg 65 : 405–413.
  59. Alvarez M, Rodriguez-Roche R, Bernardo L, Morier L, Guzman MG, 2005. Improved dengue virus plaque formation on BHK21 and LLCMK2 cells: evaluation of some factors. WHO Dengue Bull 29 : 49–57.
  60. AnandaRao R, Swaminathan S, Fernando S, Jana AM, Khanna N, 2005. A custom-designed recombinant multiepitope protein as a dengue diagnostic reagent. Protein Exp Purif 41 : 136–147.
  61. Sugrue RJ, Cui T, Xu Q, Fu J, Chan YC, 1997. The production of recombinant dengue virus E protein using Escherichia coli and Pichia pastoris. J Virol Methods 69 : 159–169.
  62. Kenney RT, Edelman R, 2003. Survey of human-use adjuvants. Expert Rev Vaccines 2 : 167–188.
  63. Simmons M, Porter KR, Hayes CG, Vaughn DW, Putnak R, 2006. Characterization of antibody responses to combinations of a dengue virus type 2 DNA vaccine and two dengue virus type 2 protein vaccines in Rhesus macaques. J Virol 80 : 9577–9585.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2008.79.353
Loading
/content/journals/10.4269/ajtmh.2008.79.353
Loading

Data & Media loading...

  • Received : 06 Jun 2007
  • Accepted : 20 Mar 2008

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error