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. 2014 Dec 24;29(6):353–363. doi: 10.1007/s12250-014-3542-7

Recent progress in dengue vaccine development

Jianchun Wei 1, Hui Chen 1,✉, Jing An 1,✉
PMCID: PMC8206420  PMID: 25547681

Abstract

Dengue virus (DENV) has four distinct serotypes. DENV infection can result in classic dengue fever and life-threatening dengue hemorrhagic fever/dengue shock syndrome. In recent decades, DENV infection has become an important public health concern in epidemic-prone areas. Vaccination is the most effective measure to prevent and control viral infections. However, several challenges impede the development of effective DENV vaccines, such as the lack of suitable animal models and the antibody-dependent enhancement phenomenon. Although no licensed DENV vaccine is available, significant progress has been made. This review summarizes candidate DENV vaccines from recent investigations.

Keywords: dengue virus, vaccine, dengue fever, flavivirus

Contributor Information

Hui Chen, Phone: +86-10-83911834, Email: chenhuicxh@ccmu.edu.cn.

Jing An, Phone: +86-10-83950107, Email: anjing@ccmu.edu.cn.

References

  1. Aihara H, Takasaki T, Toyosaki-Maeda T, Suzuki R, Okuno Y, Kurane I. T-cell activation and induction of antibodies and memory T cells by immunization with inactivated Japanese encephalitis vaccine. Viral Immunol. 2000;13:179–186. doi: 10.1089/vim.2000.13.179. [DOI] [PubMed] [Google Scholar]
  2. Anderson K B, Gibbons R V, Edelman R, Eckels K H, Putnak R J, Innis B L, Innis W S. Interference and Facilitation Between Dengue Serotypes in a Tetravalent Live Dengue Virus Vaccine Candidate. J Infect Dis. 2011;204:442–450. doi: 10.1093/infdis/jir279. [DOI] [PubMed] [Google Scholar]
  3. Arora U, Tyagi P, Swaminathan S, Khanna N. Virus-like particles displaying envelope domain III of dengue virus type 2 induce virus-specific antibody response in mice. Vaccine. 2013;31:873–878. doi: 10.1016/j.vaccine.2012.12.016. [DOI] [PubMed] [Google Scholar]
  4. Bäck A T, Lundkvist . Dengue viruses — an overview. 2013. p. 3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beckett C G, Tjaden J, Burgess T, Danko J R, Tamminga C, Simmons M, Wu S-J, Sun P, Kochel T, Raviprakash K, Hayes C G, Porter K R. Evaluation of a prototype dengue-1 DNA vaccine in a Phase 1 clinical trial. Vaccine. 2011;29:960–968. doi: 10.1016/j.vaccine.2010.11.050. [DOI] [PubMed] [Google Scholar]
  6. Bhamarapravati N, Yoksan S, Chayaniyayothin T, Angsubphakorn S, Bunyaratvej A. Immunization with a live attenuated dengue-2-virus candidate vaccine (16681-PDK 53): clinical, immunological and biological responses in adult volunteers. Bull World Health Organ. 1987;65:189–195. [PMC free article] [PubMed] [Google Scholar]
  7. Bhatt S, Gething P W, Brady O J, Messina J P, Farlow A W, Moyes C L, Drake J M, Brownstein J S, Hoen A G, Sankoh O, Myers M F, George D B, Jaenisch T, Wint G R W, Simmons C P, Scott T W, Farrar J J, Hay S I. The global distribution and burden of dengue. Nature. 2013;496:504–507. doi: 10.1038/nature12060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Blaney J E, Hanson C T, Firestone C Y, Hanley K A, Whitehead S S. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg. 2004;71:811–821. [PubMed] [Google Scholar]
  9. Blaney J E, Hanson C T, Hanley K A, Murphy B R, Whitehead S S. Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2. BMC Infect Dis. 2004;4:39. doi: 10.1186/1471-2334-4-39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Blaney J E, Sathe N S, Goddard L, Hanson C T, Romero T A, Hanley K A, Murphy B R, Whitehead S S. Dengue virus type 3 vaccine candidates generated by introduction of deletions in the 3′untranslated region (3′-UTR) or by exchange of the DENV-3 3′-UTR with that of DENV-4. Vaccine. 2008;26:817–828. doi: 10.1016/j.vaccine.2007.11.082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Brinton M A, Fernandez A V, Dispoto J H. The 3′-nucleotides of flavivirus genomic RNA form a conserved secondary structure. Virology. 1986;153:113–121. doi: 10.1016/0042-6822(86)90012-7. [DOI] [PubMed] [Google Scholar]
  12. Capeding R Z, Luna I A, Bomasang E, Lupisan S, Lang J. Liveattenuated, tetravalent dengue vaccine in children, adoles cents and adults in a dengue endemic country: randomized controlled phase I trial in the Philippines. Vaccine. 2011;29:3863–3872. doi: 10.1016/j.vaccine.2011.03.057. [DOI] [PubMed] [Google Scholar]
  13. Clements D E, Coller B A, Lieberman M M, Ogata S, Wang G, Harada K E. Development of a recombinant tetravalent dengue virus vaccine: immunogenicity and efficacy studies in mice and monkeys. Vaccine. 2010;28:2705–2715. doi: 10.1016/j.vaccine.2010.01.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Coller B A G, Clements D E, Bett A J, Sagar S L, Meulen J H T. The development of recombinant subunit envelope-based vaccines to protect against dengue virus induced disease. Vaccine. 2011;29:7267–7275. doi: 10.1016/j.vaccine.2011.07.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Durbin A P, Whitehead S S. Dengue Vaccine Candidates in Development. Curr Top Microbiol Immunol. 2010;338:129–143. doi: 10.1007/978-3-642-02215-9_10. [DOI] [PubMed] [Google Scholar]
  16. Durbin A P, Kirkpatrick B D, Pierce K K, Schmidt A C, Whitehead S S. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine. Vaccine. 2011;29:7242–7250. doi: 10.1016/j.vaccine.2011.07.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Durbin A P, Whitehead S S, McArthur J, Perreault J R, Blaney J E, Thumar B. rDEN4 Delta 30, a Live Attenuated Dengue Virus Type 4 Vaccine Candidate, Is Safe, Immunogenic, and Highly Infectious in Healthy Adult Volunteers. J Infect Dis. 2005;191:710–718. doi: 10.1086/427780. [DOI] [PubMed] [Google Scholar]
  18. Durbin A P, McArthur J H, Marron J A, Blaney J E, Thumar B, Wanionek K. rDEN2/4Delta30(ME), A Live Attenuated Chimeric Dengue Serotype 2 Vaccine Is Safe and Highly Immunogenic in Healthy Dengue-Naive Adults. Hum Vaccin. 2006;2:255–260. doi: 10.4161/hv.2.6.3494. [DOI] [PubMed] [Google Scholar]
  19. Durbin A P, Karron R A, Sun W, Vaughn D W, Reynolds M J, Murphy B R, Whitehead S S. Attenuation and immunogenicity 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. 2001;65:405–413. doi: 10.4269/ajtmh.2001.65.405. [DOI] [PubMed] [Google Scholar]
  20. Garçon N, Van Mechelen M. Recent clinical experience with vaccines using MPL- and QS-21-containing Adjuvant Systems. Expert Rev Vaccines. 2011;10:471–486. doi: 10.1586/erv.11.29. [DOI] [PubMed] [Google Scholar]
  21. Garçon N, Wettendorff M, Van Mechelen M. Role of AS04 in human papillomavirus vaccine: mode of action and clinical profile. Expert Opin Biol Ther. 2011;11:667–677. doi: 10.1517/14712598.2011.573624. [DOI] [PubMed] [Google Scholar]
  22. Guirakhoo F, Kitchener S, Morrison D, Forrat R, McCarthy K, Nichols R, Yoksan S, Duan X, Ermak T H, Kanesa-thasan N, Bedford P, Lang J, Quentin-Millet M-J, Monath T P. Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax-DEN2) vaccine: Phase I clinical trial for safety and immunogenicity: effect of yellow fever preimmunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes. Hum Vaccin. 2006;2:60–67. doi: 10.4161/hv.2.2.2555. [DOI] [PubMed] [Google Scholar]
  23. Guy B, Saville M, Lang J. Development of SanofiPasteur tetravalent dengue vaccine. Hum Vaccin. 2010;6:696–705. doi: 10.4161/hv.6.9.12739. [DOI] [PubMed] [Google Scholar]
  24. Guy B, Nougarede N, Begue S, Sanchez V, Souag N, Carre M. Cellmediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects. Vaccine. 2008;26:12–21. doi: 10.1016/j.vaccine.2007.11.068. [DOI] [PubMed] [Google Scholar]
  25. Guy B, Barrere B, Malinowski C, Saville M, Teyssou R, Lang J. From esearch to phase III: preclinical, industrial and clinical development of the SanofiPasteur tetravalent dengue vaccine. Vaccine. 2011;29:7229–7241. doi: 10.1016/j.vaccine.2011.06.094. [DOI] [PubMed] [Google Scholar]
  26. Guy B, Barban V, Mantel N, Aguirre M, Gulia S, Dumas R, Lang J. Evaluation of Interferences between Dengue Vaccine Serotypes in a Monkey Model. Am J Trop Med Hyg. 2009;80:302–311. [PubMed] [Google Scholar]
  27. Guzman M G, Harris E. The Lancet, Epub ahead of print. 2014. Dengue. [DOI] [PubMed] [Google Scholar]
  28. Guzman M G, Halstead S B, Artsob H, Buchy P, Farrar J, Gubler D J, Hunsperger E, Kroeger A, Margolis H S, Martínez E, Nathan M B, Pelegrino J L, Simmons C, Yoksan S, Peeling R W. Dengue: a continuing global threat. Nat Rev Microbiol. 2010;8:S7–S16. doi: 10.1038/nrmicro2460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Halstead S B. Studies on the attenuation of dengue 4. Asian J Infect Dis. 1978;2:112–117. [Google Scholar]
  30. Halstead S B. Controversies in dengue pathogenesis. Paediatr Int Child H. 2012;32:5–9. doi: 10.1179/2046904712Z.00000000045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Halstead S B, Heinz F X, Barrett A D T, Roehrig J T. Dengue virus: molecular basis of cell entry and pathogenesis 25–27 June 2003, Vienna, Austria. Vaccine. 2005;23:849–856. doi: 10.1016/j.vaccine.2004.03.069. [DOI] [PubMed] [Google Scholar]
  32. Halstead S B, Durbin A P, Whitehead S S, Shaffer D, Elwood D, Wanionek K, Thumar B, Blaney J E, Murphy B R, Schmidt A C. A Single Dose of the DENV-1 Candidate Vaccine rDEN1Δ30 Is Strongly Immunogenic and Induces Resistance to a Second Dose in a Randomized Trial. PLOS Negl Trop Dis. 2011;5:e1267. doi: 10.1371/journal.pntd.0001267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hanley K A, Lee J J, Blaney J E, Murphy B R, Whitehead S S. Paired charge-to-alanine mutagenesis of dengue virus type 4 NS5 generates mutants with temperature-sensitive, host range, and mouse attenuation phenotypes. J Virol. 2002;76:525–531. doi: 10.1128/JVI.76.2.525-531.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Harenberg A, Begue S, Mamessier A, Caillet C, Guy B. Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore. Hum Vacc Immunother. 2013;9:2317–2325. doi: 10.4161/hv.25562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Huang C Y, Butrapet S, Tsuchiya K R, Bhamarapravati N, Gubler D J, Kinney R M. Dengue 2 PDK-53 Virus as a Chimeric Carrier for Tetravalent Dengue Vaccine Development. J Virol. 2003;77:11436–11447. doi: 10.1128/JVI.77.21.11436-11447.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Huang C Y, Kinney R M, Livengood J A, Bolling B, Osorio J E, Stinchcomb D T. Genetic and Phenotypic Characterization of Manufacturing Seeds for a Tetravalent Dengue Vaccine (DENVax) PLOS Negl Trop Dis. 2013;7:e2243. doi: 10.1371/journal.pntd.0002243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Hui L, XiaoFeng X, Na G, An J. Preliminary evaluation of DNA vaccine candidates encoding dengue-2 prM/E and NS1: Their immunity and protective efficacy in mice. Mol Immunology. 2013;54:109–114. doi: 10.1016/j.molimm.2012.11.007. [DOI] [PubMed] [Google Scholar]
  38. Innis B L, Eckels K H. Progress in development of a liveattenuated, tetravalent dengue virus vaccine by theUnited States Army Medical Research and Materiel Command. Am J Trop Med Hyg. 2003;69:1–4. doi: 10.4269/ajtmh.2003.69.6_suppl.0690001. [DOI] [PubMed] [Google Scholar]
  39. Kitchener S, Nissen M, Nasveld P, Forrat R, Saluzzo J F. Immunogenicity and safety of two live-attenuated tetravalent dengue vaccine formulations in healthy Australian adults. Vaccine. 2006;24:1238–1241. doi: 10.1016/j.vaccine.2005.09.029. [DOI] [PubMed] [Google Scholar]
  40. Lang J. Development of SanofiPasteur tetravalent dengue vaccine. Rev Inst Med Trop Sao Paulo. 2012;54:S15–S17. doi: 10.1590/S0036-46652012000700007. [DOI] [PubMed] [Google Scholar]
  41. Leo Y S, Wilder-Smith A, Archuleta S, Shek L P, Chong C Y. Immunogenicity and safety of recombinant tetravalent dengue vaccine (CYD-TDV) in individuals aged 2–45 years Phase II randomized controlled trial in Singapore. Hum Vacc Immunother. 2012;8:1259–1271. doi: 10.4161/hv.21224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Letson G W, Singhasivanon P, Fernandez E, Abeysinghe N, Amador J J, Margolis H S, Edelman R. Dengue vaccine trial guidelines and role of large-scale, post proof-of-concept demonstration projects in bringing a dengue vaccine to use in dengue endemic areas. Human Vaccines. 2010;6:802–809. doi: 10.4161/hv.6.10.13018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lu H, Xu X, Gao N, An J. Preliminary evaluation of DNA vaccine candidates encoding dengue-2 prM/E and NS1: Their immunity and protective efficacy in mice. Molecular Immunology. 2013;54:109–114. doi: 10.1016/j.molimm.2012.11.007. [DOI] [PubMed] [Google Scholar]
  44. Mahoney R, Chocarro L, Southern J, Francis D P, Vose J, Margolis H. Dengue Vaccines Regulatory Pathways: A Report on Two Meetings with Regulators of Developing Countries. PLoS Medicine. 2011;8:e1000418. doi: 10.1371/journal.pmed.1000418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mani S, Tripathi L, Raut R, Tyagi P, Arora U, Barman T, Sood R, Galav A, Silva A D, Swaminathan S. Pichia pastoris-Expressed Dengue 2 Envelope Forms Virus-Like Particles without Pre-Membrane Protein and Induces High Titer Neutralizing Antibodies. PLoS one. 2013;8:e64595. doi: 10.1371/journal.pone.0064595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. McArthur J H, Durbin A P, Marron J A, Wanionek K A, Murphy B R, Whitehead S S. Phase I Clinical Evaluation of rDEN4Δ30-200,201: A Live Attenuated Dengue 4 Vaccine Candidate Designed for Decreased Hepatotoxicity. Am J Trop Med Hyg. 2008;79:678–684. [PMC free article] [PubMed] [Google Scholar]
  47. McKeage K, Romanowski B. AS04-adjuvanted human papillomavirus (HPV) types 16 and 18 vaccine (Cervarix®): a review of its use in the prevention of premalignant cervical lesions and cervical cancer causally related to certain oncogenic HPV types. Drugs. 2011;71:465–488. doi: 10.2165/11206820-000000000-00000. [DOI] [PubMed] [Google Scholar]
  48. McKenzie A, Watt M, Gittleson C. ISCOMATRIXTM vaccines: safety in human clinical studies. Hum Vaccin. 2010;6:237–246. doi: 10.4161/hv.6.3.10754. [DOI] [PubMed] [Google Scholar]
  49. Men R, Bray M, Clark D, Chanockrober M, Lai C-J. Dengue Type 4 Virus Mutants Containing Deletions in the 39 Noncoding Region of the RNA Genome: Analysis of Growth Restriction in Cell Culture and Altered Viremia Pattern and Immunogenicity in Rhesus Monkeys. J Virol. 1996;70:3930–3937. doi: 10.1128/jvi.70.6.3930-3937.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Morel S, Didierlaurent A, Bourguignon P, Delhaye S, Baras B, Jacob V, Planty C, Elouahabi A, Harvengt P, Carlsen H, Kielland A, Chomez P, Garçon N, Van M M. Adjuvant System AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine. 2011;29:2461–2473. doi: 10.1016/j.vaccine.2011.01.011. [DOI] [PubMed] [Google Scholar]
  51. Normile D. Surprising New Dengue Virus Throws A Spanner in Disease Control Efforts. Scinece. 2013;342:415. doi: 10.1126/science.342.6157.415. [DOI] [PubMed] [Google Scholar]
  52. Osorio J E, Brewoo J N, Silengo S J, Arguello J, Stinchcomb D T. Efficacy of a Tetravalent Chimeric Dengue Vaccine (DENVax) in Cynomolgus Macaques. Am J Trop Med Hyg. 2011;84:978–987. doi: 10.4269/ajtmh.2011.10-0592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Poo J, Galan F, Forrat R, Zambrano B, Lang J, Dayan G H. Live-attenuated tetravalent dengue vaccine in dengue-naïve children, adolescents, and adults in mexico city: randomized controlled phase 1 trial of safety and immunogenicity. Pediatr Infect Dis J. 2011;30:e9–17. doi: 10.1097/INF.0b013e3181fe05af. [DOI] [PubMed] [Google Scholar]
  54. Putnak R, Barvir D A, Burrous J M, Dubois D R, D’Andrea V M, Hoke C H, Sadoff J C, Eckels K H. Development of a Purified, Inactivated, Dengue-2 Virus Vaccine Prototype in Vero Cells: Immunogenicity and Protection in Mice and Rhesus Monkeys. J Infect Dis. 1996;174:1176–1184. doi: 10.1093/infdis/174.6.1176. [DOI] [PubMed] [Google Scholar]
  55. Raviprakash K, Porter K R, Kochel T J, Ewing D, Simmons M, Phillips I. Dengue virus type 1 DNA vaccine induces protective immune responses in rhesus macaques. J Gen Virol. 2000;81:1659–1667. doi: 10.1099/0022-1317-81-7-1659. [DOI] [PubMed] [Google Scholar]
  56. Robert Putnak J, Coller B A, Voss G, Vaughn D W, Clements D, Peters I, Bignami G, Houng H-S, Chen R C M, Barvir D A, Seriwatana J, Cayphas S, Garçon N, Gheysen D, Kanesa-thasan N, McDonell M, Humphreys T, Eckels K H, Prieels J-P, Innis B L. An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model. Vaccine. 2005;23:4442–4452. doi: 10.1016/j.vaccine.2005.03.042. [DOI] [PubMed] [Google Scholar]
  57. Rodriguez-Roche R, Gould E A. Understanding the Dengue Viruses and Progress towards Their Control. BioMed Research International. 2013;2013:690835. doi: 10.1155/2013/690835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Rothman A L. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol. 2011;11:532–543. doi: 10.1038/nri3014. [DOI] [PubMed] [Google Scholar]
  59. Sabchareon A, Lang J, Chanthavanich P, Yoksan S, Forrat R, Attanath P, Sirivichayakul C, Pengsaa K, Pojjaroen-Anant C, Chokejindachai W, Jagsudee A, Saluzzo J F, Bhamarapravati N. Safety and immunogenicity of tetravalent live-attenuated dengue vaccines in Thai adult volunteers: role of serotype concentration, ratio, and multiple doses. Am J Trop Med Hyg. 2002;66:264–272. doi: 10.4269/ajtmh.2002.66.264. [DOI] [PubMed] [Google Scholar]
  60. Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, Jiwariyavej V, Dulyachai W, Pengsaa K, Wartel T A, Moureau A, Saville M, Bouckenooghe A, Viviani S, Tornieporth N G, Lang J. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet. 2012;380:1559–1567. doi: 10.1016/S0140-6736(12)61428-7. [DOI] [PubMed] [Google Scholar]
  61. Sanchez V, Thomas G N, Tomlinson B, Chan P K S, Thomas G N. Innate and adaptive cellular immunity in flavivirus-naïve human recipients of a live-attenuated dengue serotype 3 vaccine produced in Vero cells (VDV3) Vaccine. 2006;24:4914–4926. doi: 10.1016/j.vaccine.2006.03.066. [DOI] [PubMed] [Google Scholar]
  62. Sardesai N Y, Weiner D B. Electroporation delivery of DNA vaccines: prospects for success. Curr Opin Immun. 2011;23:421–429. doi: 10.1016/j.coi.2011.03.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Simmons C P, Chau T N, Thuy T T, Tuan N M, Hoang D M, Thien N T. Maternal antibody and viral factors in the pathogenesis of dengue virus in infants. J Infect Dis. 2007;196:416–424. doi: 10.1086/519170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Simmons M, Burgess T, Lynch J, Putnak R. Protection against dengue virus by non-replicating and live attenuated vaccines used together in a prime boost vaccination strategy. Virology. 2010;396:280–288. doi: 10.1016/j.virol.2009.10.023. [DOI] [PubMed] [Google Scholar]
  65. Sinha G. Sanofi’s dengue vaccine first to complete phase 3. Nat Biotech. 2014;32:605–606. doi: 10.1038/nbt0714-605a. [DOI] [PubMed] [Google Scholar]
  66. Sun W, Nisalak A, Gettayacamin M, Eckels K H, Putnak J R, Vaughn D W, Innis B L, Thomas S J, Endy T P. Protection of Rhesus Monkeys against Dengue Virus Challenge following Tetravalent Live-attenuated Dengue Virus Vaccination. J Inf Dis. 2006;193:1658–1665. doi: 10.1086/503372. [DOI] [PubMed] [Google Scholar]
  67. Sun W, Cunningham D, Wasserman S S, Perry J, Putnak J R, Eckels K H, Vaughn D W, Thomas S J, Kanesa-Thasan N, Innis B L, Edelman R. Phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirusnaive adults. Hum Vaccin. 2009;5:33–40. doi: 10.4161/hv.5.1.6348. [DOI] [PubMed] [Google Scholar]
  68. Thisyakorn U, Thisyakorn C. Latest developments and future direction in dengue vaccines. Ther Adv Vacc. 2014;2:3–9. doi: 10.1177/2051013613507862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Thomas S J. The necessity and quandaries of dengue vaccine development. J Infect Dis. 2011;203:299–303. doi: 10.1093/infdis/jiq060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Thomas S J, Endy T P. Critical issues in dengue vaccine development. Curr Opin Infect Dis. 2011;24:442–450. doi: 10.1097/QCO.0b013e32834a1b0b. [DOI] [PubMed] [Google Scholar]
  71. Thomas S J, Eckels K H, Carletti I, Gibbons R V, Innis B L. A Phase II, Randomized, Safety and Immunogenicity Study of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Adults. Am J Trop Med Hyg. 2013;88:73–88. doi: 10.4269/ajtmh.2012.12-0361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Upasana A, Poornima T, Sathyamangalam S, Khanna N. Virus-like particles displaying envelope domain III of dengue virus type 2 induce virus-specific antibody response in mice. Vaccine. 2013;31:873–878. doi: 10.1016/j.vaccine.2012.12.016. [DOI] [PubMed] [Google Scholar]
  73. Valdés I, Hermida L, Gil L, Lazo L, Castro J, Martín J, Bernardo L, López C, Niebla O, Menéndez T, Romero Y, Sánchez J, Guzmán M G, Guillén G. Heterologous prime-boost strategy in non-human primates combining the infective dengue virus and a recombinant protein in a formulation suitable for human use. Int J Infect Dis. 2010;14:e377–e383. doi: 10.1016/j.ijid.2009.06.017. [DOI] [PubMed] [Google Scholar]
  74. Valdés I, Hermida L, Martín J, Menéndez T, Gil L, Lazo L, Castro J, Niebla O, López C, Bernardo L, Sánchez J, Romero Y, Martínez R, Guzmán M G, Guillén G. Immunological evaluation in nonhuman primates of formulations based on the chimeric protein P64k-domain III of dengue 2 and two components of Neisseria meningitidis. Vaccine. 2009;27:995–1001. doi: 10.1016/j.vaccine.2008.11.106. [DOI] [PubMed] [Google Scholar]
  75. Valdés I, Bernardo L, Gil L, Pavón A, Lazo L, López C, Romero Y, Menendez I, Falcón V, Betancourt L, Martín J, Chinea G, Silva R, Guzmán M G, Guillén G, Hermida L. A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice. Virology. 2009;394:249–258. doi: 10.1016/j.virol.2009.08.029. [DOI] [PubMed] [Google Scholar]
  76. Valdes I, Gil L, Romero Y, Castro J, Puente P, Lazo L, Marcos E, Guzman M G, Guillen G, Hermida L. The Chimeric Protein Domain III-Capsid of Dengue Virus Serotype 2 (DEN-2) Successfully Boosts Neutralizing Antibodies Generated in Monkeys upon Infection with DEN-2. Clin Vac Immun. 2011;18:455–459. doi: 10.1128/CVI.00382-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Van der Straten A, Johansen H, Rosenberg M, Sweet R W. Introduction and constitutive expression of gene products in cultured drosophila cells using hygromycin B selection. Meth Mol Cell Biol. 1989;1:1–8. doi: 10.1091/mbc.1.1.1. [DOI] [Google Scholar]
  78. Villar L, Dayan G H, Arredondo-García J L, Saville M, Noriega F. N Engl J Med. Epub ahead of print. 2014. Efficacy of a Tetravalent Dengue Vaccine in Children in Latin America. [DOI] [PubMed] [Google Scholar]
  79. Voelker R. JAMA. 2010. Race Is On for Effective Dengue Vaccine; p. 304. [DOI] [PubMed] [Google Scholar]
  80. Wahala M P B, Silva A M d. The Human Antibody Response to Dengue Virus Infection. Viruses. 2011;3:2374–2395. doi: 10.3390/v3122374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Wan S W, Lin C F, Wang S, Chen Y H, Yeh T M, Liu H S, Anderson R, Lin Y S. Current progress in dengue vaccines. J Biomed Sci. 2013;20:37. doi: 10.1186/1423-0127-20-37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Watanaveeradej V, Simasathien S, Nisalak A, Endy T P, Jarman R G, Innis B L. Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine in Flavivirus-Naive Infants. Am J Trop Med Hyg. 2011;85:341–351. doi: 10.4269/ajtmh.2011.10-0501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Whitehead S S, Hanley K A, Jr., Hanley B J E, Gilmore L E, Elkins W R, Murphy B R. Substitution of the structural genes of dengue virus type 4 with those of type 2 results in chimeric vaccine candidates which are attenuated for mosquitoes, mice, and rhesus monkeys. Vaccine. 2003;21:4307–4316. doi: 10.1016/S0264-410X(03)00488-2. [DOI] [PubMed] [Google Scholar]
  84. Whitehead S S, Falgout B, Hanley K A, Blaney J E, Markoff L, Murphy B R. A Live, Attenuated Dengue Virus Type 1 Vaccine Candidate with a 30-Nucleotide Deletion in the 3′ Untranslated Region Is Highly Attenuated and Immunogenic in Monkeys. J Virol. 2003;77:1653–1657. doi: 10.1128/JVI.77.2.1653-1657.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Wright P F, Durbin A P, Whitehead S S, Ikizler M R, Henderson S, Blaney J E. Phase 1 trial of the dengue virus type 4 vaccine candidate rDEN4{Delta}30-4995 in healthy adult volunteers. Am J Trop Med Hyg. 2009;81:834–841. doi: 10.4269/ajtmh.2009.09-0131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Zheng Q, Fan D, Gao N, An J. Evaluation of a DNA vaccine candidate expressing prM-E-NS1antigens of dengue virus serotype1with or without granulocyte-macrophagecolony-stimulating factor (GM-CSF) in immunogenicity and protection. Vaccine. 2011;29:763–771. doi: 10.1016/j.vaccine.2010.11.014. [DOI] [PubMed] [Google Scholar]

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