Volume 94, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1–4 waned during the 1–3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Article metrics loading...

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

Full text loading...



  1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI, , 2013. The global distribution and burden of dengue. Nature 496: 504507.[Crossref] [Google Scholar]
  2. Wilder-Smith A, Gubler DJ, , 2008. Geographic expansion of dengue: the impact of international travel. Med Clin North Am 92: 13771390.[Crossref] [Google Scholar]
  3. World Health Organization, 2009. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control Geneva, Switzerland: World Health Organization. [Google Scholar]
  4. Nisalak A, Endy TP, Nimmannitya S, Kalayanarooj S, Thisayakorn U, Scott RM, Burke DS, Hoke CH, Innis BL, Vaughn DW, , 2003. Serotype-specific dengue virus circulation and dengue disease in Bangkok, Thailand from 1973 to 1999. Am J Trop Med Hyg 68: 191202. [Google Scholar]
  5. Thailand Ministry of Public Health, 2013. Annual Epidemiologic Surveillance Reports. Nonthaburi, Bangkok: Bureau of Epidemiology, Department of Disease Control, 3032. [Google Scholar]
  6. Thisyakorn U, Thisyakorn C, , 2014. Latest developments and future directions in dengue vaccines. Ther Adv Vaccines 2: 39.[Crossref] [Google Scholar]
  7. Sun W, Cunningham D, Wasserman SS, Perry J, Putnak JR, Eckels KH, Vaughn DW, Thomas SJ, Kanesa-Thasan N, Innis BL, Edelman R, , 2009. Phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirus-naive adults. Hum Vaccin 5: 3340.[Crossref] [Google Scholar]
  8. Simasathien S, Thomas SJ, Watanaveeradej V, Nisalak A, Barberousse C, Innis BL, Sun W, Putnak RJ, Eckels KH, Hutagalung Y, Gibbons RV, Zhang C, De La Barrera R, Jarman RG, Chawachalasai W, Mammen MP, Jr, 2008. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus naive children. Am J Trop Med Hyg 78: 426433. [Google Scholar]
  9. Watanaveeradej V, Simasathien S, Nisalak A, Endy TP, Jarman R, Innis BL, Thomas S, Gibbons RV, Hengprasert S, Samakoses R, Kerdpanic A, Vaughn DW, Putnak R, Eckels KH, De La Barrera R, Mammen MP, Jr, 2011. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus-naive infants. Am J Trop Med Hyg 85: 341351.[Crossref] [Google Scholar]
  10. Thomas SJ, Eckels KH, Carletti I, De La Barrera R, Dessy F, Fernandez S, Putnak R, Toussaint JF, Sun W, Bauer K, Gibbons RV, Innis BL, , 2013. 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 88: 7388.[Crossref] [Google Scholar]
  11. Watanaveeradej V, Gibbons RV, Simasathien S, Nisalak A, Jarman RG, Kerdpanich A, Tournay E, De La Barrerra R, Dessy F, Toussaint JF, Eckels KH, Thomas SJ, Innis BL, , 2014. Safety and immunogenicity of a re-derived, live-attenuated dengue virus vaccine in healthy adults living in Thailand: a randomized trial. Am J Trop Med Hyg 91: 119128.[Crossref] [Google Scholar]
  12. Bauer K, Esquilin IO, Cornier AS, Thomas SJ, Quintero del Rio AI, Bertran-Pasarell J, Morales Ramirez JO, Diaz C, Carlo S, Eckels KH, Tournay E, Toussaint JF, De La Barrera R, Fernandez S, Lyons A, Sun W, Innis BL, , 2015. A phase II, randomized, safety, and immunogenicity trial of a re-derived, live-attenuated dengue virus vaccine in healthy children and adults living in Puerto Rico. Am J Trop Med Hyg 93: 441453.[Crossref] [Google Scholar]
  13. Russell PK, Nisalak A, Suhhavachana P, Vivona S, , 1967. A plaque reduction test for dengue neutralization antibodies. J Immunol 99: 285290. [Google Scholar]
  14. Crotty S, Aubert RD, Glidewell J, Ahmed R, , 2004. Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system. J Immunol Methods 286: 111122.[Crossref] [Google Scholar]
  15. Moris P, van der Most R, Leroux-Roels I, Clement F, Dramé M, Hanon E, Leroux-Roels GG, Van Mechelen M, , 2011. H5N1 influenza vaccine formulated with AS03A induces strong cross-reactive and polyfunctional CD4 T cell responses. J Clin Immunol 31: 443454.[Crossref] [Google Scholar]
  16. Sadon N, Delers A, Jarman RG, Klungthong C, Nisalak A, Gibbons RV, Vassilev V, , 2008. A new quantitative RT-PCR method for sensitive detection of dengue virus in serum samples. J Virol Methods 153: 16.[Crossref] [Google Scholar]
  17. Libraty DH, Acosta LP, Tallo V, Segubre-Mercado E, Bautista A, Potts JA, Jarman RG, Yoon IK, Gibbons RV, Brion JD, Capeding RZ, , 2009. A prospective nested case-control study of dengue in infants: rethinking and refining the antibody-dependent enhancement dengue hemorrhagic fever model. PLoS Med 6: e1000171.[Crossref] [Google Scholar]
  18. Chanthavanich P, Luxemburger C, Sirivichayakul C, Lapphra K, Pengsaa K, Sutee Yoksan S, Arunee Sabchareon A, Lang J, , 2006. Immune response and occurrence of dengue infection in Thai children three to eight years after vaccination with live attenuated tetravalent dengue vaccine. Am J Trop Med Hyg 75: 2628. [Google Scholar]

Data & Media loading...

Supplementary PDF

  • Received : 10 Sep 2015
  • Accepted : 29 Feb 2016
  • Published online : 01 Jun 2016

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