Volume 79, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The rDEN4Δ30-200,201 is a live attenuated DENV-4 vaccine candidate specifically designed to further attenuate the rDEN4Δ30 parent virus. In the present study, 28 healthy adult volunteers were randomized to receive either 10 plaque-forming unit (PFU) of vaccine (20) or placebo (8) as a single subcutaneous injection. Volunteers were evaluated for safety every other day for 16 days. Serum neutralizing antibody titer against DEN4 was determined at study day 28, 42, and 180. The vaccine infected all vaccinees and was well tolerated without inducing alanine aminotransferase (ALT) elevations. Although virus was not recovered from the serum of any vaccinee, moderate levels of neutralizing antibody were induced in all volunteers. Thus the restricted replication of rDEN4Δ30-200,201 previously documented in animal models was confirmed in humans. The rDEN4Δ30-200,201 is a promising candidate and can be considered for inclusion in a tetravalent dengue virus (DENV) vaccine.


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  1. Suaya JA, Shepard DS, Beatty ME, 2006. Dengue: Burden of Disease and Costs of Illness. Scientific Working Group on Dengue—2006 Report. Geneva: WHO, 35–49.
  2. Mathers CD, Ezzati M, Lopez AD, 2007. Measuring the burden of neglected tropical diseases: the global burden of disease framework. PLoS Negl Trop Dis 1 : e114.
  3. World Health Organization, 1997. Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. Geneva: WHO.
  4. Sabin A, 1952. Research on dengue during World War II. Am J Trop Med Hyg 1 : 30–50.
  5. Okuno Y, Fukunaga T, Tadano M, Fukai K, Ikeda T, Sekii K, Ariyoshi H, 1983. Serological studies on volunteers inoculated experimentally with a dengue virus strain in 1943. Biken J 26 : 161–163.
  6. Papaevangelou G, Halstead SB, 1977. Infections with two dengue viruses in Greece in the 20th century. Did dengue hemorrhagic fever occur in the 1928 epidemic? Am J Trop Med Hyg 80 : 46–51.
  7. Burke DS, Nisalak A, Johnson DE, Scott RM, 1988. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 38 : 172–180.
  8. Kliks SC, Nisalak A, Brandt WE, Wahl L, Burke DS, 1989. Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg 40 : 444–451.
  9. Whitehead SS, Blaney JE, Durbin AP, Murphy BR, 2007. Prospects for a dengue virus vaccine. Nat Rev Microbiol 5 : 518–528.
  10. Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS, 2006. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol 19 : 10–32.
  11. Durbin AP, Karron RA, Sun W, Vaughn DW, Reynolds MJ, Perreault JR, Thumar B, Men R, Lai CJ, Elkins WR, Chanock RM, Murphy BR, Whitehead SS, 2001. 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 65 : 405–413.
  12. Durbin AP, McArthur J, Marron JA, Blaney JE Jr, Thumar B, Wanionek K, Murphy BR, Whitehead SS, 2006. The live attenuated dengue serotype 1 vaccine rDEN1Delta30 is safe and highly immunogenic in healthy adult volunteers. Hum Vaccin 2 : 167–173.
  13. Durbin AP, McArthur JH, Marron JA, Blaney JE, Thumar B, Wanionek K, Murphy BR, Whitehead SS, 2006. rDEN2/4Delta30(ME), a live attenuated chimeric dengue serotype 2 vaccine is safe and highly immunogenic in healthy dengue-naive adults. Hum Vaccin 2 : 255–260.
  14. Durbin AP, Whitehead SS, McArthur J, Perreault JR, Blaney JE Jr, Thumar B, Murphy BR, Karron RA, 2005. 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 191 : 710–718.
  15. Kanesa-thasan N, Sun W, Kim-Ahn G, Van Albert S, Putnak JR, King A, Raengsakulsrach B, Christ-Schmidt H, Gilson K, Zahradnik JM, Vaughn DW, Innis BL, Saluzzo JF, Hoke CH Jr, 2001. Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers. Vaccine 19 : 3179–3188.
  16. Vaughn DW, Hoke CH Jr, Yoksan S, LaChance R, Innis BL, Rice RM, Bhamarapravati N, 1996. Testing of a dengue 2 live-attenuated vaccine (strain 16681 PDK 53) in ten American volunteers. Vaccine 14 : 329–336.
  17. Eckels KH, Scott RM, Bancroft WH, Brown J, Dubois DR, Summers PL, Russell PK, Halstead SB, 1984. Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. V. Human response to immunization with a candidate vaccine prepared in fetal rhesus lung cells. Am J Trop Med Hyg 33 : 684–689.
  18. Edelman R, Tacket CO, Wasserman SS, Vaughn DW, Eckels KH, Dubois DR, Summers PL, Hoke CH, 1994. A live attenuated dengue-1 vaccine candidate (45AZ5) passaged in primary dog kidney cell culture is attenuated and immunogenic for humans. J Infect Dis 170 : 1448–1455.
  19. Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S, Kunentrasai N, Viramitrachai W, Ratanachueke S, Kiatpolpoj S, Innis BL, Rothman AL, Nisalak A, Ennis FA, 1997. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 176 : 313–321.
  20. Kuo CH, Tai DI, Chang Chien CS, Lan CK, Chiou SS, Liaw YF, 1992. Liver biochemical tests and dengue fever. Am J Trop Med Hyg 47 : 265–270.
  21. Mohan B, Patwari AK, Anand VK, 2000. Hepatic dysfunction in childhood dengue infection. J Trop Pediatr 46 : 40–43.
  22. Wahid SF, Sanusi S, Zawawi MM, Ali RA, 2000. A comparison of the pattern of liver involvement in dengue hemorrhagic fever with classic dengue fever. Southeast Asian J Trop Med Public Health 31 : 259–263.
  23. Liu HW, Ho TL, Hwang CS, Liao YH, 1989. Clinical observations of virologically confirmed dengue fever in the 1987 outbreak in southern Taiwan. Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 5 : 42–49.
  24. Lin YL, Liu CC, Lei HY, Yeh TM, Lin YS, Chen RM, Liu HS, 2000. Infection of five human liver cell lines by dengue-2 virus. J Med Virol 60 : 425–431.
  25. Hanley KA, Lee JJ, Blaney JE Jr, Murphy BR, Whitehead SS, 2002. Paired charge-to-alanine mutagenesis of dengue virus type 4 NS5 generates mutants with temperature-sensitive, host range, and mouse attenuation phenotypes. J Virol 76 : 525–531.
  26. 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 : 3440–3448.
  27. Troyer JM, Hanley KA, Whitehead SS, Strickman D, Karron RA, Durbin AP, Murphy BR, 2001. A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes. Am J Trop Med Hyg 65 : 414–419.

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  • Received : 01 Apr 2008
  • Accepted : 30 Jun 2008

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