Volume 85, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



A dengue vaccine effective against all four serotypes is urgently needed. However, safety and immunogenicity could be affected by prior exposure to flaviviruses. This open, controlled, phase IIa study was conducted in 35 healthy adults who had received monovalent, live attenuated Vero cell-derived dengue vaccine against dengue virus 1 (VDV1) or 2 (VDV2) or yellow fever (YF) vaccine 1 year before or who were flavivirus-naïve. All participants received one subcutaneous injection of tetravalent dengue vaccine (TDV) and were followed for 180 days. Previous vaccination did not increase reactogenicity, laboratory abnormalities, or incidence of vaccine viremia, but it did increase the neutralizing antibody response to dengue virus that persisted at day 180. There was no increase in YF antibodies in participants previously immunized with YF vaccine. Prior exposure to YF or monovalent dengue vaccines had no adverse effects on the safety or incidence of viremia associated with this TDV, but it increased immunogenicity.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Green S, Rothman A, , 2006. Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Curr Opin Infect Dis 19: 429436.[Crossref] [Google Scholar]
  2. Kurane I, , 2007. Dengue hemorrhagic fever with special emphasis on immunopathogenesis. Comp Immunol Microbiol Infect Dis 30: 329340.[Crossref] [Google Scholar]
  3. 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: 54775485.[Crossref] [Google Scholar]
  4. 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 immunogenicity in nonhuman primates of a chimeric yellow fever-dengue virus tetravalent vaccine. J Virol 75: 72907304.[Crossref] [Google Scholar]
  5. Guy B, Guirakhoo F, Barban V, Higgs S, Monath TP, Lang J, , 2010. Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses. Vaccine 28: 632649.[Crossref] [Google Scholar]
  6. Morrison D, Legg TJ, Billings CW, Forrat R, Yoksan S, Lang J, , 2010. A novel tetravalent dengue vaccine is well tolerated and immunogenic against all four serotypes in Flavivirus-naive adults. J Infect Dis 201: 370377.[Crossref] [Google Scholar]
  7. 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 (ChimeriVax-DEN2) vaccine: phase I clinical trial for safety and immunogenicity. Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes. Hum Vaccin 2: 6067.[Crossref] [Google Scholar]
  8. Monath TP, McCarthy K, Bedford P, Johnson CT, Nichols R, Yoksan S, Marchesani R, Knauber M, Wells KH, Arroyo J, Guirakhoo F, , 2002. Clinical proof of principle for ChimeriVax: recombinant live, attenuated vaccines against flavivirus infections. Vaccine 20: 10041018.[Crossref] [Google Scholar]
  9. Guy B, Nougarede N, Begue S, Sanchez V, Souag N, Carre M, Chambonneau L, Morrisson DN, Shaw D, Qiao M, Dumas R, Lang J, Forrat R, , 2008. Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects. Vaccine 26: 57125721.[Crossref] [Google Scholar]
  10. Sanchez V, Gimenez S, Tomlinson B, Chan P, Thomas N, Forrat R, Chambonneau L, Lang J, Guy B, , 2006. Innate and adaptive cellular immunity in flavivirus-naive human recipients of a live-attenuated dengue serotype 3 vaccine produced in Vero cells (VDV3). Vaccine 24: 49144926.[Crossref] [Google Scholar]
  11. Mantel N, Aguirre M, Gulia S, Girerd-Chambaz Y, Colombani S, Moste C, Barban V, , 2008. Standardized quantitative RT-PCR assays for quantitation of yellow fever and chimeric yellow fever-dengue vaccines. J Virol Methods 151: 4046.[Crossref] [Google Scholar]
  12. Porterfield JS, , 1959. A plaque technique for the titration of yellow fever virus and antisera. Trans R Soc Trop Med Hyg 53: 458466.[Crossref] [Google Scholar]
  13. Roehrig JT, Hombach J, Barrett AD, , 2008. Guidelines for plaque-reduction neutralization testing of human antibodies to dengue viruses. Viral Immunol 21: 123132.[Crossref] [Google Scholar]
  14. 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: 302311. [Google Scholar]
  15. Poo J, Galan F, Forrat R, Zambrano B, Lang J, Dayan GH, , 2011. Live-attenuated tetravalent dengue vaccine in dengue-naive children, adolescents, and adults in Mexico City: randomized controlled phase 1 trial of safety and immunogenicity. Pediatr Infect Dis J 30: e9e17. doi:10.1097/INF.0b013e3181fe05af.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 03 Aug 2010
  • Accepted : 04 Apr 2011
  • Published online : 01 Oct 2011

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