Skip to main content
SpringerLink
Log in

Animal Models for Dengue and Zika Vaccine Development

  • Chapter
  • First Online:
Dengue and Zika: Control and Antiviral Treatment Strategies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1062))

Abstract

The current status of animal models in the study of dengue and Zika are covered in this review. Mouse models deficient in IFN signaling are used to overcome the natural resistance of mice to non-encephalitic flaviviruses. Conditional IFNAR mice and non-human primates (NHP) are useful immuno-competent models. Sterile immunity after dengue vaccination is not observed in NHPs. Placental and fetal development in NHPs is similar to humans, facilitating studies on infection-mediated fetal impairment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aguirre S, Maestre AM, Pagni S, Patel JR, Savage T, Gutman D, Maringer K, Bernal-Rubio D, Shabman RS, Simon V, Rodriguez-Madoz JR, Mulder LC, Barber GN, Fernandez-Sesma A (2012) DENV inhibits type I IFN production in infected cells by cleaving human STING. PLoS Pathog 8(10):e1002934. https://doi.org/10.1371/journal.ppat.1002934

    Article  PubMed  PubMed Central  Google Scholar 

  2. Aliota MT, Caine EA, Walker EC, Larkin KE, Camacho E, Osorio JE (2016) Characterization of Lethal Zika Virus Infection in AG129 Mice. PLoS Negl Trop Dis 10(4):e0004682. https://doi.org/10.1371/journal.pntd.0004682

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Amanna IJ, Slifka MK (2014) Current trends in West Nile virus vaccine development. Expert Rev Vaccines 13(5):589–608. https://doi.org/10.1586/14760584.2014.906309

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. An J, Kimura-Kuroda J, Hirabayashi Y, Yasui K (1999) Development of a novel mouse model for dengue virus infection. Virology 263(1):70–77. https://doi.org/10.1006/viro.1999.9887

    Article  PubMed  CAS  Google Scholar 

  5. Angsubhakorn S, Yoksan S, Pradermwong A, Nitatpattana N, Sahaphong S, Bhamarapravati N (1994) Dengue-3 (16562) PGMK 33 vaccine: neurovirulence, viremia and immune responses in Macaca fascicularis. Southeast Asian J Trop Med Public Health 25(3):554–559

    PubMed  CAS  Google Scholar 

  6. Ashour J, Morrison J, Laurent-Rolle M, Belicha-Villanueva A, Plumlee CR, Bernal-Rubio D, Williams KL, Harris E, Fernandez-Sesma A, Schindler C, Garcia-Sastre A (2010) Mouse STAT2 restricts early dengue virus replication. Cell Host Microbe 8(5):410–421. https://doi.org/10.1016/j.chom.2010.10.007. S1931-3128(10)00344-6 [pii]

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Atrasheuskaya A, Petzelbauer P, Fredeking TM, Ignatyev G (2003) Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection. FEMS Immunol Med Microbiol 35(1):33–42

    Article  CAS  PubMed  Google Scholar 

  8. Balsitis SJ, Williams KL, Lachica R, Flores D, Kyle JL, Mehlhop E, Johnson S, Diamond MS, Beatty PR, Harris E (2010) Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification. PLoS Pathog 6(2):e1000790. https://doi.org/10.1371/journal.ppat.1000790

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Becker R (2016) Missing link: animal models to study whether Zika causes birth defects. Nat Med 22(3):225–227. https://doi.org/10.1038/nm0316-225

    Article  PubMed  CAS  Google Scholar 

  10. Bente DA, Melkus MW, Garcia JV, Rico-Hesse R (2005) Dengue fever in humanized NOD/SCID mice. J Virol 79(21):13797–13799. https://doi.org/10.1128/JVI.79.21.13797-13799.2005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Bernardo L, Fleitas O, Pavon A, Hermida L, Guillen G, Guzman MG (2009) Antibodies induced by dengue virus type 1 and 2 envelope domain III recombinant proteins in monkeys neutralize strains with different genotypes. Clin Vaccine Immunol 16(12):1829–1831. https://doi.org/10.1128/CVI.00191-09

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Bernardo L, Hermida L, Martin J, Alvarez M, Prado I, Lopez C, Martinez R, Rodriguez-Roche R, Zulueta A, Lazo L, Rosario D, Guillen G, Guzman MG (2008a) Anamnestic antibody response after viral challenge in monkeys immunized with dengue 2 recombinant fusion proteins. Arch Virol 153(5):849–854. https://doi.org/10.1007/s00705-008-0050-9

    Article  PubMed  CAS  Google Scholar 

  13. Bernardo L, Izquierdo A, Alvarez M, Rosario D, Prado I, Lopez C, Martinez R, Castro J, Santana E, Hermida L, Guillen G, Guzman MG (2008b) Immunogenicity and protective efficacy of a recombinant fusion protein containing the domain III of the dengue 1 envelope protein in non-human primates. Antiviral Res 80(2):194–199. https://doi.org/10.1016/j.antiviral.2008.06.005

    Article  PubMed  CAS  Google Scholar 

  14. Bernardo L, Izquierdo A, Prado I, Rosario D, Alvarez M, Santana E, Castro J, Martinez R, Rodriguez R, Morier L, Guillen G, Guzman MG (2008c) Primary and secondary infections of Macaca fascicularis monkeys with Asian and American genotypes of dengue virus 2. Clin Vaccine Immunol 15(3):439–446. https://doi.org/10.1128/CVI.00208-07

    Article  PubMed  CAS  Google Scholar 

  15. Blaney JE Jr, Hanson CT, Firestone CY, Hanley KA, Murphy BR, Whitehead SS (2004a) Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg 71(6):811–821

    Article  PubMed  CAS  Google Scholar 

  16. Blaney JE Jr, Hanson CT, Hanley KA, Murphy BR, Whitehead SS (2004b) Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2. BMC Infect Dis 4:39. https://doi.org/10.1186/1471-2334-4-39

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Bournazos S, DiLillo DJ, Ravetch JV (2015) The role of Fc-FcgammaR interactions in IgG-mediated microbial neutralization. J Exp Med 212(9):1361–1369. https://doi.org/10.1084/jem.20151267

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Bowie AG, Unterholzner L (2008) Viral evasion and subversion of pattern-recognition receptor signalling. Nat Rev Immunol 8(12):911–922. https://doi.org/10.1038/nri2436

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Brasil P, Pereira JP Jr, Raja Gabaglia C, Damasceno L, Wakimoto M, Ribeiro Nogueira RM, Carvalho de Sequeira P, Machado Siqueira A, Abreu de Carvalho LM, Cotrim da Cunha D, Calvet GA, Neves ES, Moreira ME, Rodrigues Baiao AE, Nassar de Carvalho PR, Janzen C, Valderramos SG, Cherry JD, Bispo de Filippis AM, Nielsen-Saines K (2016) Zika Virus infection in pregnant women in Rio de Janeiro – preliminary report. N Engl J Med. https://doi.org/10.1056/NEJMoa1602412

  20. Bray M, Men R, Lai CJ (1996) Monkeys immunized with intertypic chimeric dengue viruses are protected against wild-type virus challenge. J Virol 70(6):4162–4166

    PubMed  PubMed Central  CAS  Google Scholar 

  21. Brewoo JN, Kinney RM, Powell TD, Arguello JJ, Silengo SJ, Partidos CD, Huang CY, Stinchcomb DT, Osorio JE (2011) Immunogenicity and efficacy of chimeric dengue vaccine (DENVax) formulations in interferon-deficient AG129 mice. Vaccine. https://doi.org/10.1016/j.vaccine.2011.11.072

  22. Brewoo JN, Kinney RM, Powell TD, Arguello JJ, Silengo SJ, Partidos CD, Huang CY, Stinchcomb DT, Osorio JE (2012) Immunogenicity and efficacy of chimeric dengue vaccine (DENVax) formulations in interferon-deficient AG129 mice. Vaccine 30(8):1513–1520. https://doi.org/10.1016/j.vaccine.2011.11.072

    Article  PubMed  CAS  Google Scholar 

  23. Butrapet S, Rabablert J, Angsubhakorn S, Wiriyarat W, Huang C, Kinney R, Punyim S, Bhamarapravati N (2002) Chimeric dengue type 2/type 1 viruses induce immune responses in cynomolgus monkeys. Southeast Asian J Trop Med Public Health 33(3):589–599

    PubMed  CAS  Google Scholar 

  24. Calvert AE, Huang CY, Kinney RM, Roehrig JT (2006) Non-structural proteins of dengue 2 virus offer limited protection to interferon-deficient mice after dengue 2 virus challenge. J Gen Virol 87(Pt 2):339–346. https://doi.org/10.1099/vir.0.81256-0

    Article  PubMed  CAS  Google Scholar 

  25. Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J, Dub T, Baudouin L, Teissier A, Larre P, Vial AL, Decam C, Choumet V, Halstead SK, Willison HJ, Musset L, Manuguerra JC, Despres P, Fournier E, Mallet HP, Musso D, Fontanet A, Neil J, Ghawche F (2016) Guillain-Barre syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 387(10027):1531–1539. https://doi.org/10.1016/S0140-6736(16)00562-6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Chan KW, Watanabe S, Kavishna R, Alonso S, Vasudevan SG (2015) Animal models for studying dengue pathogenesis and therapy. Antiviral Res 123:5–14. https://doi.org/10.1016/j.antiviral.2015.08.013

    Article  PubMed  CAS  Google Scholar 

  27. Chen HC, Hofman FM, Kung JT, Lin YD, Wu-Hsieh BA (2007a) Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. J Virol 81(11):5518–5526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chen HC, Lai SY, Sung JM, Lee SH, Lin YC, Wang WK, Chen YC, Kao CL, King CC, Wu-Hsieh BA (2004) Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus. J Med Virol 73(3):419–431

    Article  PubMed  Google Scholar 

  29. Chen L, Ewing D, Subramanian H, Block K, Rayner J, Alterson KD, Sedegah M, Hayes C, Porter K, Raviprakash K (2007b) A heterologous DNA prime-Venezuelan equine encephalitis virus replicon particle boost dengue vaccine regimen affords complete protection from virus challenge in cynomolgus macaques. J Virol 81(21):11634–11639. https://doi.org/10.1128/JVI.00996-07

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Chen ST, Lin YL, Huang MT, Wu MF, Cheng SC, Lei HY, Lee CK, Chiou TW, Wong CH, Hsieh SL (2008) CLEC5A is critical for dengue-virus-induced lethal disease. Nature 453(7195):672–676

    Article  CAS  PubMed  Google Scholar 

  31. Clements DE, Coller BA, Lieberman MM, Ogata S, Wang G, Harada KE, Putnak JR, Ivy JM, McDonell M, Bignami GS, Peters ID, Leung J, Weeks-Levy C, Nakano ET, Humphreys T (2010) Development of a recombinant tetravalent dengue virus vaccine: immunogenicity and efficacy studies in mice and monkeys. Vaccine 28(15):2705–2715. https://doi.org/10.1016/j.vaccine. S0264-410X(10)00054-X [pii]

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Cox J, Mota J, Sukupolvi-Petty S, Diamond MS, Rico-Hesse R (2012) Mosquito bite delivery of dengue virus enhances immunogenicity and pathogenesis in humanized mice. J Virol 86(14):7637–7649. https://doi.org/10.1128/JVI.00534-12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Dick GW (1952) Zika virus. II. Pathogenicity and physical properties. Trans R Soc Trop Med Hyg 46(5):521–534

    Article  CAS  PubMed  Google Scholar 

  34. Dick GW, Kitchen SF, Haddow AJ (1952) Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg 46(5):509–520

    Article  CAS  PubMed  Google Scholar 

  35. Domnich A, Panatto D, Arbuzova EK, Signori A, Avio U, Gasparini R, Amicizia D (2014) Immunogenicity against Far Eastern and Siberian subtypes of tick-borne encephalitis (TBE) virus elicited by the currently available vaccines based on the European subtype: systematic review and meta-analysis. Hum Vaccin Immunother 10(10):2819–2833. https://doi.org/10.4161/hv.29984

    Article  PubMed  PubMed Central  Google Scholar 

  36. Dowall SD, Graham VA, Rayner E, Atkinson B, Hall G, Watson RJ, Bosworth A, Bonney LC, Kitchen S, Hewson R (2016) A susceptible mouse model for Zika Virus infection. PLoS Negl Trop Dis 10(5):e0004658. https://doi.org/10.1371/journal.pntd.0004658

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Dowd KA, Ko SY, Morabito KM, Yang ES, Pelc RS, DeMaso CR, Castilho LR, Abbink P, Boyd M, Nityanandam R, Gordon DN, Gallagher JR, Chen X, Todd JP, Tsybovsky Y, Harris A, Huang YS, Higgs S, Vanlandingham DL, Andersen H, Lewis MG, De La Barrera R, Eckels KH, Jarman RG, Nason MC, Barouch DH, Roederer M, Kong WP, Mascola JR, Pierson TC, Graham BS (2016) Rapid development of a DNA vaccine for Zika virus. Science 354(6309):237–240. https://doi.org/10.1126/science.aai9137

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Driggers RW, Ho CY, Korhonen EM, Kuivanen S, Jaaskelainen AJ, Smura T, Rosenberg A, Hill DA, DeBiasi RL, Vezina G, Timofeev J, Rodriguez FJ, Levanov L, Razak J, Iyengar P, Hennenfent A, Kennedy R, Lanciotti R, du Plessis A, Vapalahti O (2016) Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med 374(22):2142–2151. https://doi.org/10.1056/NEJMoa1601824

    Article  PubMed  CAS  Google Scholar 

  39. Dudley DM, Aliota MT, Mohr EL, Weiler AM, Lehrer-Brey G, Weisgrau KL, Mohns MS, Breitbach ME, Rasheed MN, Newman CM, Gellerup DD, Moncla LH, Post J, Schultz-Darken N, Schotzko ML, Hayes JM, Eudailey JA, Moody MA, Permar SR, O’Connor SL, Rakasz EG, Simmons HA, Capuano S, Golos TG, Osorio JE, Friedrich TC, O’Connor DH (2016) A rhesus macaque model of Asian-lineage Zika virus infection. Nat Commun 7:12204. https://doi.org/10.1038/ncomms12204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Eckels KH, Dubois DR, Putnak R, Vaughn DW, Innis BL, Henchal EA, Hoke CH Jr (2003) Modification of dengue virus strains by passage in primary dog kidney cells: preparation of candidate vaccines and immunization of monkeys. Am J Trop Med Hyg 69(6 Suppl):12–16

    Article  PubMed  Google Scholar 

  41. Eckels KH, Dubois DR, Summers PL, Schlesinger JJ, Shelly M, Cohen S, Zhang YM, Lai CJ, Kurane I, Rothman A et al (1994) Immunization of monkeys with baculovirus-dengue type-4 recombinants containing envelope and nonstructural proteins: evidence of priming and partial protection. Am J Trop Med Hyg 50(4):472–478

    Article  CAS  PubMed  Google Scholar 

  42. Engelmann F, Josset L, Girke T, Park B, Barron A, Dewane J, Hammarlund E, Lewis A, Axthelm MK, Slifka MK, Messaoudi I (2014) Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model. PLoS Negl Trop Dis 8(11):e3295. https://doi.org/10.1371/journal.pntd.0003295

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. WHO Strategic Advisory Group of Experts (2016) Dengue vaccine. Wkly Epidemiol Rec 91(21):282–284

    Google Scholar 

  44. Fernandez S, Thomas SJ, De La Barrera R, Im-Erbsin R, Jarman RG, Baras B, Toussaint JF, Mossman S, Innis BL, Schmidt A, Malice MP, Festraets P, Warter L, Putnak JR, Eckels KH (2015) An adjuvanted, tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques. Am J Trop Med Hyg 92(4):698–708. https://doi.org/10.4269/ajtmh.14-0268

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Frias-Staheli N, Dorner M, Marukian S, Billerbeck E, Labitt RN, Rice CM, Ploss A (2014) Utility of humanized BLT mice for analysis of dengue virus infection and antiviral drug testing. J Virol 88(4):2205–2218. https://doi.org/10.1128/JVI.03085-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Fuchs J, Chu H, O’Day P, Pyles R, Bourne N, Das SC, Milligan GN, Barrett AD, Partidos CD, Osorio JE (2014) Investigating the efficacy of monovalent and tetravalent dengue vaccine formulations against DENV-4 challenge in AG129 mice. Vaccine 32(48):6537–6543. https://doi.org/10.1016/j.vaccine.2014.08.087

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Galler R, Marchevsky RS, Caride E, Almeida LF, Yamamura AM, Jabor AV, Motta MC, Bonaldo MC, Coutinho ES, Freire MS (2005) Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys. Braz J Med Biol Res 38(12):1835–1846. S0100-879X2005001200012

    Article  CAS  PubMed  Google Scholar 

  48. Girschick HJ, Grammer AC, Nanki T, Mayo M, Lipsky PE (2001) RAG1 and RAG2 expression by B cell subsets from human tonsil and peripheral blood. J Immunol 166(1):377–386

    Article  CAS  PubMed  Google Scholar 

  49. Govindarajan D, Meschino S, Guan L, Clements DE, ter Meulen JH, Casimiro DR, Coller BA, Bett AJ (2015) Preclinical development of a dengue tetravalent recombinant subunit vaccine: immunogenicity and protective efficacy in nonhuman primates. Vaccine 33(33):4105–4116. https://doi.org/10.1016/j.vaccine.2015.06.067

    Article  PubMed  CAS  Google Scholar 

  50. Guirakhoo F, Pugachev K, Arroyo J, Miller C, Zhang ZX, Weltzin R, Georgakopoulos K, Catalan J, Ocran S, Draper K, Monath TP (2002) Viremia and immunogenicity in nonhuman primates of a tetravalent yellow fever-dengue chimeric vaccine: genetic reconstructions, dose adjustment, and antibody responses against wild-type dengue virus isolates. Virology 298(1):146–159. https://doi.org/10.1006/viro.2002.1462. S0042682202914625 [pii]

    Article  PubMed  CAS  Google Scholar 

  51. Guirakhoo F, Pugachev K, Zhang Z, Myers G, Levenbook I, Draper K, Lang J, Ocran S, Mitchell F, Parsons M, Brown N, Brandler S, Fournier C, Barrere B, Rizvi F, Travassos A, Nichols R, Trent D, Monath T (2004a) Safety and efficacy of chimeric yellow fever-dengue virus tetravalent vaccine formulations in nonhuman primates. J Virol 78(9):4761–4775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Guirakhoo F, Weltzin R, Chambers TJ, Zhang ZX, Soike K, Ratterree M, Arroyo J, Georgakopoulos K, Catalan J, Monath TP (2000) Recombinant chimeric yellow fever-dengue type 2 virus is immunogenic and protective in nonhuman primates. J Virol 74(12):5477–5485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Guirakhoo F, Zhang Z, Myers G, Johnson BW, Pugachev K, Nichols R, Brown N, Levenbook I, Draper K, Cyrek S, Lang J, Fournier C, Barrere B, Delagrave S, Monath TP (2004b) A single amino acid substitution in the envelope protein of chimeric yellow fever-dengue 1 vaccine virus reduces neurovirulence for suckling mice and viremia/viscerotropism for monkeys. J Virol 78(18):9998–10008. https://doi.org/10.1128/JVI.78.18.9998-10008.2004. 78/18/9998 [pii]

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Guy B, Barban V, Mantel N, Aguirre M, Gulia S, Pontvianne J, Jourdier TM, Ramirez L, Gregoire V, Charnay C, Burdin N, Dumas R, Lang J (2009) Evaluation of interferences between dengue vaccine serotypes in a monkey model. Am J Trop Med Hyg 80(2):302–311

    Article  PubMed  Google Scholar 

  55. Guzman MG, Rodriguez R, Rodriguez R, Hermida L, Alvarez M, Lazo L, Mune M, Rosario D, Valdes K, Vazquez S, Martinez R, Serrano T, Paez J, Espinosa R, Pumariega T, Guillen G (2003) Induction of neutralizing antibodies and partial protection from viral challenge in Macaca fascicularis immunized with recombinant dengue 4 virus envelope glycoprotein expressed in Pichia pastoris. Am J Trop Med Hyg 69(2):129–134

    Article  PubMed  CAS  Google Scholar 

  56. Hadinegoro SR, Arredondo-Garcia JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, Hj Muhammad HI, Ismail HR, Limkittikul K, Rivera-Medina DM, Tran HN, Bouckenooghe A, Chansinghakul D, Cortes M, Fanouillere K, Forrat R, Frago C, Gailhardou S, Jackson N, Noriega F, Plennevaux E, Wartel TA, Zambrano B, Saville M, Cyd-Tdv Dengue Vaccine Working Group (2015) Efficacy and long-term safety of a dengue vaccine in regions of endemic disease. N Engl J Med 373(13):1195–1206. https://doi.org/10.1056/NEJMoa1506223

    Article  PubMed  CAS  Google Scholar 

  57. Hanley KA, Manlucu LR, Manipon GG, Hanson CT, Whitehead SS, Murphy BR, Blaney JE Jr (2004) Introduction of mutations into the non-structural genes or 3′ untranslated region of an attenuated dengue virus type 4 vaccine candidate further decreases replication in rhesus monkeys while retaining protective immunity. Vaccine 22(25-26):3440–3448. https://doi.org/10.1016/j.vaccine.2004.02.031

    Article  PubMed  CAS  Google Scholar 

  58. Hermida L, Bernardo L, Martin J, Alvarez M, Prado I, Lopez C, Sierra Bde L, Martinez R, Rodriguez R, Zulueta A, Perez AB, Lazo L, Rosario D, Guillen G, Guzman MG (2006) A recombinant fusion protein containing the domain III of the dengue-2 envelope protein is immunogenic and protective in nonhuman primates. Vaccine 24(16):3165–3171. https://doi.org/10.1016/j.vaccine.2006.01.036

    Article  PubMed  CAS  Google Scholar 

  59. Honda K, Taniguchi T (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6(9):644–658. https://doi.org/10.1038/nri1900

    Article  PubMed  CAS  Google Scholar 

  60. Huang CY, Butrapet S, Tsuchiya KR, Bhamarapravati N, Gubler DJ, Kinney RM (2003) Dengue 2 PDK-53 virus as a chimeric carrier for tetravalent dengue vaccine development. J Virol 77(21):11436–11447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Huang KJ, Li SY, Chen SC, Liu HS, Lin YS, Yeh TM, Liu CC, Lei HY (2000) Manifestation of thrombocytopenia in dengue-2-virus-infected mice. J Gen Virol 81(Pt 9):2177–2182. https://doi.org/10.1099/0022-1317-81-9-2177

    Article  PubMed  CAS  Google Scholar 

  62. Ivashkiv LB, Donlin LT (2014) Regulation of type I interferon responses. Nat Rev Immunol 14(1):36–49. https://doi.org/10.1038/nri3581

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Izquierdo A, Bernardo L, Martin J, Santana E, Hermida L, Guillen G, Guzman MG (2008) Serotype-specificity of recombinant fusion proteins containing domain III of dengue virus. Virus Res 138(1-2):135–138. https://doi.org/10.1016/j.virusres.2008.08.008

    Article  PubMed  CAS  Google Scholar 

  64. Jaiswal S, Pazoles P, Woda M, Shultz LD, Greiner DL, Brehm MA, Mathew A (2012) Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice. Immunology 136(3):334–343. https://doi.org/10.1111/j.1365-2567.2012.03585.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Jaiswal S, Pearson T, Friberg H, Shultz LD, Greiner DL, Rothman AL, Mathew A (2009) Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice. PLoS One 4(10):e7251. https://doi.org/10.1371/journal.pone.0007251

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Johnson AJ, Roehrig JT (1999) New mouse model for dengue virus vaccine testing. J Virol 73(1):783–786

    PubMed  PubMed Central  CAS  Google Scholar 

  67. Kariko K, Buckstein M, Ni H, Weissman D (2005) Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23(2):165–175. https://doi.org/10.1016/j.immuni.2005.06.008

    Article  PubMed  CAS  Google Scholar 

  68. Kim E, Erdos G, Huang S, Kenniston T, Falo LD Jr, Gambotto A (2016) Preventative vaccines for Zika Virus outbreak: preliminary evaluation. EBioMedicine. https://doi.org/10.1016/j.ebiom.2016.09.028

    Article  PubMed  PubMed Central  Google Scholar 

  69. Koraka P, Benton S, van Amerongen G, Stittelaar KJ, Osterhaus AD (2007) Efficacy of a live attenuated tetravalent candidate dengue vaccine in naive and previously infected cynomolgus macaques. Vaccine 25(29):5409–5416. https://doi.org/10.1016/j.vaccine.2007.04.079

    Article  PubMed  Google Scholar 

  70. Kuruvilla JG, Troyer RM, Devi S, Akkina R (2007) Dengue virus infection and immune response in humanized RAG2(-/-)gamma(c)(-/-) (RAG-hu) mice. Virology 369(1):143–152

    Article  CAS  PubMed  Google Scholar 

  71. Larocca RA, Abbink P, Peron JP, Zanotto PM, Iampietro MJ, Badamchi-Zadeh A, Boyd M, Ng’ang’a D, Kirilova M, Nityanandam R, Mercado NB, Li Z, Moseley ET, Bricault CA, Borducchi EN, Giglio PB, Jetton D, Neubauer G, Nkolola JP, Maxfield LF, De La Barrera RA, Jarman RG, Eckels KH, Michael NL, Thomas SJ, Barouch DH (2016) Vaccine protection against Zika virus from Brazil. Nature 536(7617):474–478. https://doi.org/10.1038/nature18952

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Lazear HM, Govero J, Smith AM, Platt DJ, Fernandez E, Miner JJ, Diamond MS (2016) A mouse model of Zika Virus Pathogenesis. Cell Host Microbe 19(5):720–730. https://doi.org/10.1016/j.chom.2016.03.010

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Lee YR, Hu HY, Kuo SH, Lei HY, Lin YS, Yeh TM, Liu CC, Liu HS (2013) Dengue virus infection induces autophagy: an in vivo study. J Biomed Sci 20:65. https://doi.org/10.1186/1423-0127-20-65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Lee YR, Huang KJ, Lei HY, Chen SH, Lin YS, Yeh TM, Liu HS (2005) Suckling mice were used to detect infectious dengue-2 viruses by intracerebral injection of the full-length RNA transcript. Intervirology 48(2-3):161–166. https://doi.org/10.1159/000081744

    Article  PubMed  CAS  Google Scholar 

  75. Li XF, Deng YQ, Yang HQ, Zhao H, Jiang T, Yu XD, Li SH, Ye Q, Zhu SY, Wang HJ, Zhang Y, Ma J, Yu YX, Liu ZY, Li YH, Qin ED, Shi PY, Qin CF (2013) A chimeric dengue virus vaccine using Japanese encephalitis virus vaccine strain SA14-14-2 as backbone is immunogenic and protective against either parental virus in mice and nonhuman primates. J Virol 87(24):13694–13705. https://doi.org/10.1128/JVI.00931-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Li XF, Dong HL, Huang XY, Qiu YF, Wang HJ, Deng YQ, Zhang NN, Ye Q, Zhao H, Liu ZY, Fan H, An XP, Sun SH, Gao B, Fa YZ, Tong YG, Zhang FC, Gao GF, Cao WC, Shi PY, Qin CF (2016) Characterization of a 2016 clinical isolate of Zika Virus in Non-human Primates. EBioMedicine 12:170–177. https://doi.org/10.1016/j.ebiom.2016.09.022

    Article  PubMed  PubMed Central  Google Scholar 

  77. Li X, Leung S, Qureshi S, Darnell JE Jr, Stark GR (1996) Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha. J Biol Chem 271(10):5790–5794

    Article  CAS  PubMed  Google Scholar 

  78. Lin YL, Liao CL, Chen LK, Yeh CT, Liu CI, Ma SH, Huang YY, Huang YL, Kao CL, King CC (1998) Study of Dengue virus infection in SCID mice engrafted with human K562 cells. J Virol 72(12):9729–9737

    PubMed  PubMed Central  CAS  Google Scholar 

  79. Lum LC, Lam SK, Choy YS, George R, Harun F (1996) Dengue encephalitis: a true entity? Am J Trop Med Hyg 54(3):256–259

    Article  CAS  PubMed  Google Scholar 

  80. Marchette NJ, Dubois DR, Larsen LK, Summers PL, Kraiselburd EG, Gubler DJ, Eckels KH (1990) Preparation of an attenuated dengue 4 (341750 Carib) virus vaccine. I. pre-clinical studies. Am J Trop Med Hyg 43(2):212–218

    Article  CAS  PubMed  Google Scholar 

  81. Marcos E, Gil L, Lazo L, Izquierdo A, Brown E, Suzarte E, Valdes I, Garcia A, Mendez L, Guzman MG, Guillen G, Hermida L (2013) Purified and highly aggregated chimeric protein DIIIC-2 induces a functional immune response in mice against dengue 2 virus. Arch Virol 158(1):225–230. https://doi.org/10.1007/s00705-012-1471-z

    Article  PubMed  CAS  Google Scholar 

  82. Markoff L, Pang X, Houng Hs HS, Falgout B, Olsen R, Jones E, Polo S (2002) Derivation and characterization of a dengue type 1 host range-restricted mutant virus that is attenuated and highly immunogenic in monkeys. J Virol 76(7):3318–3328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. McBurney SP, Sunshine JE, Gabriel S, Huynh JP, Sutton WF, Fuller DH, Haigwood NL, Messer WB (2016) Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates. Vaccine 34(30):3500–3507. https://doi.org/10.1016/j.vaccine.2016.03.108

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Men R, Bray M, Clark D, Chanock RM, Lai CJ (1996) Dengue type 4 virus mutants containing deletions in the 3′ noncoding region of the RNA genome: analysis of growth restriction in cell culture and altered viremia pattern and immunogenicity in rhesus monkeys. J Virol 70(6):3930–3937

    PubMed  PubMed Central  CAS  Google Scholar 

  85. 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 Ankara expressing a truncated envelope glycoprotein of dengue type 2 virus induced resistance to dengue type 2 virus challenge. Vaccine 18(27):3113–3122

    Article  CAS  PubMed  Google Scholar 

  86. Milligan GN, Sarathy VV, Infante E, Li L, Campbell GA, Beatty PR, Harris E, Barrett AD, Bourne N (2015) A dengue virus type 4 model of disseminated Lethal Infection in AG129 Mice. PLoS One 10(5):e0125476. https://doi.org/10.1371/journal.pone.0125476

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Mladinich KM, Piaskowski SM, Rudersdorf R, Eernisse CM, Weisgrau KL, Martins MA, Furlott JR, Partidos CD, Brewoo JN, Osorio JE, Wilson NA, Rakasz EG, Watkins DI (2012) Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques. Immunogenetics 64(2):111–121. https://doi.org/10.1007/s00251-011-0566-0

    Article  PubMed  CAS  Google Scholar 

  88. Mota J, Rico-Hesse R (2009) Humanized mice show clinical signs of dengue fever according to infecting virus genotype. J Virol 83(17):8638–8645. https://doi.org/10.1128/JVI.00581-09

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Mota J, Rico-Hesse R (2011) Dengue virus tropism in humanized mice recapitulates human dengue fever. PLoS One 6(6):e20762. https://doi.org/10.1371/journal.pone.0020762

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Nguyen SM, Antony KM, Dudley DM, Kohn S, Simmons HA, Wolfe B, Salamat MS, Teixeira LBC, Wiepz GJ, Thoong TH, Aliota MT, Weiler AM, Barry GL, Weisgrau KL, Vosler LJ, Mohns MS, Breitbach ME, Stewart LM, Rasheed MN, Newman CM, Graham ME, Wieben OE, Turski PA, Johnson KM, Post J, Hayes JM, Schultz-Darken N, Schotzko ML, Eudailey JA, Permar SR, Rakasz EG, Mohr EL, Capuano S 3rd, Tarantal AF, Osorio JE, O’Connor SL, Friedrich TC, O’Connor DH, Golos TG (2017) Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques. PLoS Pathog 13(5):e1006378. https://doi.org/10.1371/journal.ppat.1006378

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Oehler E, Watrin L, Larre P, Leparc-Goffart I, Lastere S, Valour F, Baudouin L, Mallet H, Musso D, Ghawche F (2014) Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013. Euro Surveill 19(9)

    Google Scholar 

  92. Omatsu T, Moi ML, Hirayama T, Takasaki T, Nakamura S, Tajima S, Ito M, Yoshida T, Saito A, Katakai Y, Akari H, Kurane I (2011) Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: development of high levels of viraemia and demonstration of protective immunity. J Gen Virol 92(Pt 10):2272–2280. https://doi.org/10.1099/vir.0.031229-0

    Article  PubMed  CAS  Google Scholar 

  93. Orozco S, Schmid MA, Parameswaran P, Lachica R, Henn MR, Beatty R, Harris E (2012) Characterization of a model of lethal dengue virus 2 infection in C57BL/6 mice deficient in the alpha/beta interferon receptor. J Gen Virol 93(Pt 10):2152–2157. https://doi.org/10.1099/vir.0.045088-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Osorio JE, Brewoo JN, Silengo SJ, Arguello J, Moldovan IR, Tary-Lehmann M, Powell TD, Livengood JA, Kinney RM, Huang CY, Stinchcomb DT (2011) Efficacy of a tetravalent chimeric dengue vaccine (DENVax) in Cynomolgus macaques. Am J Trop Med Hyg 84(6):978–987. https://doi.org/10.4269/ajtmh.2011.10-0592

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Paes MV, Pinhao AT, Barreto DF, Costa SM, Oliveira MP, Nogueira AC, Takiya CM, Farias-Filho JC, Schatzmayr HG, Alves AM, Barth OM (2005) Liver injury and viremia in mice infected with dengue-2 virus. Virology 338(2):236–246. https://doi.org/10.1016/j.virol.2005.04.042

    Article  PubMed  CAS  Google Scholar 

  96. Patey O, Ollivaud L, Breuil J, Lafaix C (1993) Unusual neurologic manifestations occurring during dengue fever infection. Am J Trop Med Hyg 48(6):793–802

    Article  CAS  PubMed  Google Scholar 

  97. Pentsuk N, van der Laan JW (2009) An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol 86(4):328–344. https://doi.org/10.1002/bdrb.20201

    Article  PubMed  CAS  Google Scholar 

  98. Perry ST, Buck MD, Lada SM, Schindler C, Shresta S (2011) STAT2 mediates innate immunity to Dengue virus in the absence of STAT1 via the type I interferon receptor. PLoS Pathog 7(2):e1001297. https://doi.org/10.1371/journal.ppat.1001297

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Perry ST, Prestwood TR, Lada SM, Benedict CA, Shresta S (2009) Cardif-mediated signaling controls the initial innate response to dengue virus in vivo. J Virol 83(16):8276–8281. https://doi.org/10.1128/JVI.00365-09

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Pinto AK, Brien JD, Lam CY, Johnson S, Chiang C, Hiscott J, Sarathy VV, Barrett AD, Shresta S, Diamond MS (2015) Defining new therapeutics using a more immunocompetent mouse model of antibody-enhanced Dengue Virus infection. MBio 6(5):e01316–e01315. https://doi.org/10.1128/mBio.01316-15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Platanias LC (2005) Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5(5):375–386. https://doi.org/10.1038/nri1604

    Article  CAS  PubMed  Google Scholar 

  102. Porter KR, Ewing D, Chen L, Wu SJ, Hayes CG, Ferrari M, Teneza-Mora N, Raviprakash K (2012) Immunogenicity and protective efficacy of a vaxfectin-adjuvanted tetravalent dengue DNA vaccine. Vaccine 30(2):336–341. https://doi.org/10.1016/j.vaccine.2011.10.085

    Article  PubMed  CAS  Google Scholar 

  103. Prestwood TR, Morar MM, Zellweger RM, Miller R, May MM, Yauch LE, Lada SM, Shresta S (2012) Gamma interferon (IFN-gamma) receptor restricts systemic dengue virus replication and prevents paralysis in IFN-alpha/beta receptor-deficient mice. J Virol 86(23):12561–12570. https://doi.org/10.1128/JVI.06743-11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Putnak R, Barvir DA, Burrous JM, Dubois DR, D’Andrea VM, Hoke CH, Sadoff JC, Eckels KH (1996) Development of a purified, inactivated, dengue-2 virus vaccine prototype in Vero cells: immunogenicity and protection in mice and rhesus monkeys. J Infect Dis 174(6):1176–1184

    Article  CAS  PubMed  Google Scholar 

  105. Putnak R, Fuller J, VanderZanden L, Innis BL, Vaughn DW (2003) Vaccination of rhesus macaques against dengue-2 virus with a plasmid DNA vaccine encoding the viral pre-membrane and envelope genes. Am J Trop Med Hyg 68(4):469–476

    Article  PubMed  CAS  Google Scholar 

  106. Raviprakash K, Apt D, Brinkman A, Skinner C, Yang S, Dawes G, Ewing D, Wu SJ, Bass S, Punnonen J, Porter K (2006) A chimeric tetravalent dengue DNA vaccine elicits neutralizing antibody to all four virus serotypes in rhesus macaques. Virology 353(1):166–173. https://doi.org/10.1016/j.virol.2006.05.005

    Article  PubMed  CAS  Google Scholar 

  107. Raviprakash K, Porter KR, Kochel TJ, Ewing D, Simmons M, Phillips I, Murphy GS, Weiss WR, Hayes CG (2000) Dengue virus type 1 DNA vaccine induces protective immune responses in rhesus macaques. J Gen Virol 81(Pt 7):1659–1667. https://doi.org/10.1099/0022-1317-81-7-1659

    Article  PubMed  CAS  Google Scholar 

  108. Raviprakash K, Wang D, Ewing D, Holman DH, Block K, Woraratanadharm J, Chen L, Hayes C, Dong JY, Porter K (2008) A tetravalent dengue vaccine based on a complex adenovirus vector provides significant protection in rhesus monkeys against all four serotypes of dengue virus. J Virol 82(14):6927–6934. https://doi.org/10.1128/JVI.02724-07

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Robert Putnak J, Coller BA, Voss G, Vaughn DW, Clements D, Peters I, Bignami G, Houng HS, Chen RC, Barvir DA, Seriwatana J, Cayphas S, Garcon N, Gheysen D, Kanesa-Thasan N, McDonell M, Humphreys T, Eckels KH, Prieels JP, Innis BL (2005) An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model. Vaccine 23(35):4442–4452. https://doi.org/10.1016/j.vaccine.2005.03.042

    Article  PubMed  CAS  Google Scholar 

  110. Rossi SL, Tesh RB, Azar SR, Muruato AE, Hanley KA, Auguste AJ, Langsjoen RM, Paessler S, Vasilakis N, Weaver SC (2016) Characterization of a novel murine model to Study Zika Virus. Am J Trop Med Hyg 94(6):1362–1369. https://doi.org/10.4269/ajtmh.16-0111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Sarathy VV, Infante E, Li L, Campbell GA, Wang T, Paessler S, Robert Beatty P, Harris E, Milligan GN, Bourne N, Barrett AD (2015a) Characterization of lethal dengue virus type 4 (DENV-4) TVP-376 infection in mice lacking both IFN-alpha/beta and IFN-gamma receptors (AG129) and comparison with the DENV-2 AG129 mouse model. J Gen Virol 96(10):3035–3048. https://doi.org/10.1099/jgv.0.000246

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Sarathy VV, White M, Li L, Gorder SR, Pyles RB, Campbell GA, Milligan GN, Bourne N, Barrett AD (2015b) A lethal murine infection model for dengue virus 3 in AG129 mice deficient in type I and II interferon receptors leads to systemic disease. J Virol 89(2):1254–1266. https://doi.org/10.1128/JVI.01320-14

    Article  PubMed  CAS  Google Scholar 

  113. Sariol CA, White LJ (2014) Utility, limitations, and future of non-human primates for dengue research and vaccine development. Front Immunol 5:452. https://doi.org/10.3389/fimmu.2014.00452

    Article  PubMed  PubMed Central  Google Scholar 

  114. Sarno M, Sacramento GA, Khouri R, do Rosario MS, Costa F, Archanjo G, Santos LA, Nery N Jr, Vasilakis N, Ko AI, de Almeida AR (2016) Zika Virus infection and stillbirths: A case of Hydrops Fetalis, Hydranencephaly and Fetal Demise. PLoS Negl Trop Dis 10(2):e0004517. https://doi.org/10.1371/journal.pntd.0004517

    Article  PubMed  PubMed Central  Google Scholar 

  115. Schul W, Liu W, Xu HY, Flamand M, Vasudevan SG (2007) A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. J Infect Dis 195(5):665–674

    Article  CAS  PubMed  Google Scholar 

  116. Shan C, Muruato AE, Nunes BTD, Luo H, Xie X, Medeiros DBA, Wakamiya M, Tesh RB, Barrett AD, Wang T, Weaver SC, Vasconcelos PFC, Rossi SL, Shi PY (2017) A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models. Nat Med 23(6):763–767. https://doi.org/10.1038/nm.4322

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  117. Shi P-Y (2012) Molecular Virology and Control of Flaviviruses. Caister Academic Press, Norfolk

    Google Scholar 

  118. Shresta S, Kyle JL, Robert Beatty P, Harris E (2004a) Early activation of natural killer and B cells in response to primary dengue virus infection in A/J mice. Virology 319(2):262–273

    Article  CAS  PubMed  Google Scholar 

  119. Shresta S, Kyle JL, Snider HM, Basavapatna M, Beatty PR, Harris E (2004b) Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical. J Virol 78(6):2701–2710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Shresta S, Sharar KL, Prigozhin DM, Beatty PR, Harris E (2006) Murine model for dengue virus-induced lethal disease with increased vascular permeability. J Virol 80(20):10208–10217. 80/20/10208 [pii] 1261128/JVI.00062-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Shresta S, Sharar KL, Prigozhin DM, Snider HM, Beatty PR, Harris E (2005) Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary dengue virus infection in mice. J Immunol 175(6):3946–3954

    Article  CAS  PubMed  Google Scholar 

  122. Simmons M, Burgess T, Lynch J, Putnak R (2010) Protection against dengue virus by non-replicating and live attenuated vaccines used together in a prime boost vaccination strategy. Virology 396(2):280–288. https://doi.org/10.1016/j.virol.2009.10.023

    Article  PubMed  CAS  Google Scholar 

  123. 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(19):9577–9585. https://doi.org/10.1128/JVI.00284-06

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Sridharan A, Chen Q, Tang KF, Ooi EE, Hibberd ML, Chen J (2013) Inhibition of megakaryocyte development in the bone marrow underlies dengue virus-induced thrombocytopenia in humanized mice. J Virol 87(21):11648–11658. https://doi.org/10.1128/JVI.01156-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. St John AL, Rathore AP, Raghavan B, Ng ML, Abraham SN (2013) Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage. Elife 2:e00481. https://doi.org/10.7554/eLife.00481

    Article  PubMed  PubMed Central  Google Scholar 

  126. Strouts FR, Popper SJ, Partidos CD, Stinchcomb DT, Osorio JE, Relman DA (2016) Early transcriptional signatures of the immune response to a live attenuated Tetravalent Dengue Vaccine candidate in Non-human Primates. PLoS Negl Trop Dis 10(5):e0004731. https://doi.org/10.1371/journal.pntd.0004731

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Sumathy K, Kulkarni B, Gondu RK, Ponnuru SK, Bonguram N, Eligeti R, Gadiyaram S, Praturi U, Chougule B, Karunakaran L, Ella KM (2017) Protective efficacy of Zika vaccine in AG129 mouse model. Sci Rep 7:46375. https://doi.org/10.1038/srep46375

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Sun W, Nisalak A, Gettayacamin M, Eckels KH, Putnak JR, Vaughn DW, Innis BL, Thomas SJ, Endy TP (2006) Protection of Rhesus monkeys against dengue virus challenge after tetravalent live attenuated dengue virus vaccination. J Infect Dis 193(12):1658–1665. https://doi.org/10.1086/503372

    Article  PubMed  Google Scholar 

  129. Suphatrakul A, Yasanga T, Keelapang P, Sriburi R, Roytrakul T, Pulmanausahakul R, Utaipat U, Kawilapan Y, Puttikhunt C, Kasinrerk W, Yoksan S, Auewarakul P, Malasit P, Charoensri N, Sittisombut N (2015) Generation and preclinical immunogenicity study of dengue type 2 virus-like particles derived from stably transfected mosquito cells. Vaccine 33(42):5613–5622. https://doi.org/10.1016/j.vaccine.2015.08.090

    Article  PubMed  CAS  Google Scholar 

  130. Tan GK, Ng JK, Trasti SL, Schul W, Yip G, Alonso S (2010) A non mouse-adapted dengue virus strain as a new model of severe dengue infection in AG129 mice. PLoS Negl Trop Dis 4(4):e672. https://doi.org/10.1371/journal.pntd.0000672

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Valdes I, Bernardo L, Gil L, Pavon A, Lazo L, Lopez C, Romero Y, Menendez I, Falcon V, Betancourt L, Martin J, Chinea G, Silva R, Guzman MG, Guillen G, Hermida L (2009) 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 394(2):249–258. https://doi.org/10.1016/j.virol. S0042-6822(09)00517-0 [pii]

    Article  PubMed  CAS  Google Scholar 

  132. Vasconcelos PF, Monath TP (2016) Yellow Fever remains a potential threat to public health. Vector Borne Zoonotic Dis 16(8):566–567. https://doi.org/10.1089/vbz.2016.2031

    Article  PubMed  Google Scholar 

  133. Vaughan K, Greenbaum J, Blythe M, Peters B, Sette A (2010) Meta-analysis of all immune epitope data in the Flavivirus genus: inventory of current immune epitope data status in the context of virus immunity and immunopathology. Viral Immunol 23(3):259–284. https://doi.org/10.1089/vim.2010.0006

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Velzing J, Groen J, Drouet MT, van Amerongen G, Copra C, Osterhaus AD, Deubel V (1999) Induction of protective immunity against Dengue virus type 2: comparison of candidate live attenuated and recombinant vaccines. Vaccine 17(11-12):1312–1320

    Article  CAS  PubMed  Google Scholar 

  135. Ventura CV, Maia M, Bravo-Filho V, Gois AL, Belfort R Jr (2016) Zika virus in Brazil and macular atrophy in a child with microcephaly. Lancet 387(10015):228. https://doi.org/10.1016/S0140-6736(16)00006-4

    Article  PubMed  Google Scholar 

  136. Waddell LA, Greig JD (2016) Scoping review of the Zika Virus Literature. PLoS One 11(5):e0156376. https://doi.org/10.1371/journal.pone.0156376

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Wang SY, Cheng XH, Li JX, Li XY, Zhu FC, Liu P (2015) Comparing the immunogenicity and safety of 3 Japanese encephalitis vaccines in Asia-Pacific area: a systematic review and meta-analysis. Hum Vaccin Immunother 11(6):1418–1425. https://doi.org/10.1080/21645515.2015.1011996

    Article  PubMed  PubMed Central  Google Scholar 

  138. Whitehead SS, Falgout B, Hanley KA, Blaney Jr JE Jr, Markoff L, Murphy BR (2003a) 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 77(2):1653–1657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Whitehead SS, Hanley KA, Blaney JE Jr, Gilmore LE, Elkins WR, Murphy BR (2003b) 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 21(27-30):4307–4316

    Article  CAS  PubMed  Google Scholar 

  140. Wu KY, Zuo GL, Li XF, Ye Q, Deng YQ, Huang XY, Cao WC, Qin CF, Luo ZG (2016) Vertical transmission of Zika virus targeting the radial glial cells affects cortex development of offspring mice. Cell Res 26(6):645–654. https://doi.org/10.1038/cr.2016.58

    Article  PubMed  PubMed Central  Google Scholar 

  141. Yauch LE, Zellweger RM, Kotturi MF, Qutubuddin A, Sidney J, Peters B, Prestwood TR, Sette A, Shresta S (2009) A protective role for dengue virus-specific CD8+ T cells. J Immunol 182(8):4865–4873

    Article  CAS  PubMed  Google Scholar 

  142. Yin Z, Chen YL, Schul W, Wang QY, Gu F, Duraiswamy J, Kondreddi RR, Niyomrattanakit P, Lakshminarayana SB, Goh A, Xu HY, Liu W, Liu B, Lim JY, Ng CY, Qing M, Lim CC, Yip A, Wang G, Chan WL, Tan HP, Lin K, Zhang B, Zou G, Bernard KA, Garrett C, Beltz K, Dong M, Weaver M, He H, Pichota A, Dartois V, Keller TH, Shi PY (2009) An adenosine nucleoside inhibitor of dengue virus. Proc Natl Acad Sci U S A 106(48):20435–20439. https://doi.org/10.1073/pnas.0907010106

    Article  PubMed  PubMed Central  Google Scholar 

  143. Yoneyama M, Fujita T (2007) Function of RIG-I-like receptors in antiviral innate immunity. J Biol Chem 282(21):15315–15318. https://doi.org/10.1074/jbc.R700007200

    Article  PubMed  CAS  Google Scholar 

  144. Yu CY, Chang TH, Liang JJ, Chiang RL, Lee YL, Liao CL, Lin YL (2012) Dengue virus targets the adaptor protein MITA to subvert host innate immunity. PLoS Pathog 8(6):e1002780. https://doi.org/10.1371/journal.ppat.1002780

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Zellweger RM, Eddy WE, Tang WW, Miller R, Shresta S (2014) CD8+ T cells prevent antigen-induced antibody-dependent enhancement of dengue disease in mice. J Immunol 193(8):4117–4124. https://doi.org/10.4049/jimmunol.1401597

    Article  PubMed  CAS  Google Scholar 

  146. Zellweger RM, Prestwood TR, Shresta S (2010) Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease. Cell Host Microbe 7(2):128–139. https://doi.org/10.1016/j.chom. S1931-3128(10)00030-2 [pii]

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Zellweger RM, Shresta S (2014) Mouse models to study dengue virus immunology and pathogenesis. Front Immunol 5:151. https://doi.org/10.3389/fimmu.2014.00151

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  148. Zmurko J, Marques RE, Schols D, Verbeken E, Kaptein SJ, Neyts J (2016) The viral polymerase inhibitor 7-deaza-2′-c-methyladenosine is a potent inhibitor of in vitro Zika virus replication and delays disease progression in a robust mouse infection model. PLoS Negl Trop Dis 10(5):e0004695. https://doi.org/10.1371/journal.pntd.0004695

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Zust R, Dong H, Li XF, Chang DC, Zhang B, Balakrishnan T, Toh YX, Jiang T, Li SH, Deng YQ, Ellis BR, Ellis EM, Poidinger M, Zolezzi F, Qin CF, Shi PY, Fink K (2013) Rational design of a live attenuated dengue vaccine: 2′-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques. PLoS Pathog 9(8):e1003521. https://doi.org/10.1371/journal.ppat.1003521

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Züst R, Dong H, Li XF, Chang DC, Zhang B, Balakrishnan T, Toh YX, Jiang T, Li SH, Deng YQ, Ellis BR, Ellis EM, Poidinger M, Zolezzi F, Qin CF, Shi PY, Fink K (2013) Rational design of a live attenuated dengue vaccine: 2′-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques. PLoS Pathog 9(8):e1003521. https://doi.org/10.1371/journal.ppat.1003521

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  151. Zust R, Toh YX, Valdes I, Cerny D, Heinrich J, Hermida L, Marcos E, Guillen G, Kalinke U, Shi PY, Fink K (2014) Type I interferon signals in macrophages and dendritic cells control dengue virus infection: implications for a new mouse model to test dengue vaccines. J Virol 88(13):7276–7285. https://doi.org/10.1128/JVI.03827-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Singapore Immunology Network, Agency for Science, Technology and Research A*STAR, Singapore, Singapore

    Eduardo Alves dos Santos & Katja Fink

Authors
  1. Eduardo Alves dos Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katja Fink
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katja Fink .

Editor information

Editors and Affiliations

  1. Institute of Biochemistry, University of Lübeck, Lübeck, Germany

    Rolf Hilgenfeld

  2. Emerging Infectious Diseases Program, Duke-NUS Medical School Singapore, Singapore, Singapore

    Subhash G. Vasudevan

Discussion of Chapter 16 in Dengue and Zika: Control and Antiviral Treatment Strategies

Discussion of Chapter 16 in Dengue and Zika: Control and Antiviral Treatment Strategies

This discussion was held at the 2nd Advanced Study Week on Emerging Viral Diseases at Praia do Tofo, Mozambique.Transcribed by Hilgenfeld R and Vasudevan SG (Eds); approved by Dr. Katja Fink for the presentation of the topic on “Measuring antibody-mediated protection after dengue vaccination with in vitro assays and animal models”. However, because animal models are widely used in the study of Dengue and Zika and wanted to present the current status in the monograph we invited Dr. Fink to prepare a review of the topic and provide comprehensive references for the various animal models used by researchers. We however not that the discussion touched on some important points on antibody neutralization that are relevant and have decided to present Dr. Fink’s abstract and the discussion.

16.1.1 Measuring Antibody-Mediated Protection After Dengue Vaccination with In Vitro Assays and Animal Models

  • Katja Fink 

Dengue vaccine development and related research has brought a wealth of new knowledge about the relevance of innate and adaptive components of the immune response after dengue virus infection. There is evidence from human challenge studies that dengue neutralizing antibody titers correlate with protection. However, this rule does not seem to be true for prospective natural infection studies, and one reason for conflicting results may be the usage of different assays to measure neutralizing antibodies. In fact, a standard readout to measure a protective immune response is still not defined for dengue. Using examples from our vaccine development and therapeutic antibody studies I will provide an overview of dengue and zika animal models that are useful to measure protective immune -, and in particular, protective antibody responses.

  • Joanna Miller: Your skin-derived macrophages were a really nice model to analyze antibody ADE and neutralization. Have you tried maturing monocytes from blood and using them as a model as well?

  • Katja Fink: No, and the reason for that is first because we had the skin assay already set up and the skin is a really a good source of macrophages and DCs. We also know that in the in vitro differentiation setting, surface markers get down-regulated or upregulated and it is quite difficult to compare this to primary cells. We want to have an assay that closely reflects the situation in vivo.

  • Vijay Dhanasekaran: This is more of a general question in terms of understanding the differences between animal models. Particularly referring to the studies carried out by a Cambridge group (Smith DJ & colleagues) trying to understand the antigenic variation of Dengue viruses, which was published in Science last year [2015 Sep 18;349(6254):1338–43]. They showed a huge difference in polyclonal responses to the same Dengue serotype. And this was much lesser than that exhibited between Dengue serotypes. I was wondering if you had any insight into why they exhibited such a difference and I think that study was done in macaques.

  • Katja Fink: Did you say that the antigenic variations were studied in macaques? I’m not familar with that work.

  • Vijay Dhanasekaran: The actual response there was a huge antigenic variation between different strains of the same type. But when compared between types, the differences are much lesser.

  • Aravinda de Silva: Maybe I can comment on this. The point of the study is that certain strains of Dengue within a serotype are very different from one another with respect to neutralization and that they are closer to another serotype. So that study is looking at the viruses that were outliers. I think we have to be very cautious about how we interpret that study, some of these outlier strains are heavily cell-type passaged strains. As Félix Rey mentioned yesterday, a single mutation within the E protein can change the breathing structure of the viruses and just make them more broadly susceptible to neutralization. So I think, I would’nt draw a conclusion from the published study that in nature serotypes will behave that way. The authors of the study may disagree with me.

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Alves dos Santos, E., Fink, K. (2018). Animal Models for Dengue and Zika Vaccine Development. In: Hilgenfeld, R., Vasudevan, S. (eds) Dengue and Zika: Control and Antiviral Treatment Strategies. Advances in Experimental Medicine and Biology, vol 1062. Springer, Singapore. https://doi.org/10.1007/978-981-10-8727-1_16

Download citation

Publish with us

Policies and ethics

Search

Navigation