1921
Live-attenuated dengue vaccine development
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

We describe the results of initial safety testing of 10 live-attenuated dengue virus (DENV) vaccine candidates modified by serial passage in primary dog kidney (PDK) cells at the Walter Reed Army Institute of Research. The Phase 1 studies, conducted in 65 volunteers, were designed to select an attenuated vaccine candidate for each DENV serotype. No recipient of the DENV candidate vaccines sustained serious injury or required treatment. Three vaccine candidates were associated with transient idiosyncratic reactions in one volunteer each, resulting in their withdrawal from further clinical development. Increasing PDK cell passage of DENV-1, DENV-2, and DENV-3 candidate vaccines increased attenuation for volunteers, yet also decreased infectivity and immunogenicity. This effect was less clear for DENV-4 candidate vaccines following 15 and 20 PDK cell passages. Only one passage level each of the tested DENV-2, -3, and -4 vaccine candidates was judged acceptably reactogenic and suitable for expanded clinical study. Subsequent studies with more recipients will further establish safety and immunogenicity of the four selected vaccine candidates: DENV-1 45AZ5 PDK 20, DENV-2 S16803 PDK 50, DENV-3 CH53489 PDK 20, and DENV-4 341750 PDK 20.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2003.69.17
2003-12-01
2017-11-22
Loading full text...

Full text loading...

/deliver/fulltext/14761645/69/6_suppl/0690017.html?itemId=/content/journals/10.4269/ajtmh.2003.69.17&mimeType=html&fmt=ahah

References

  1. Bancroft WH, Scott RM, Eckels KH, Hoke CH Jr, Simms TE, Jesrani KD, Summers PL, Dubois DR, Tsoulos D, Russell PK, 1984. Dengue virus type 2 vaccine: reactogenicity and immunogenicity in soldiers. J Infect Dis 149 : 1005–1010.
  2. Bhamarapravati N, Yoksan S, 2000. Live attenuated tetravalent dengue vaccine. Vaccine 18 (suppl 2): 44–47.
  3. Halstead SB, Deen J, 2002. The future of dengue vaccines. Lancet 360 : 1243–1245.
  4. Bancroft WH, Eckels KH, Brandt WE, 1986. Human responses to live candidate dengue vaccines. Fukai K, ed. Virus Vaccines in Asian Countries. Tokyo: University of Tokyo Press, 169–175.
  5. Kanesa-thasan N, Putnak R, Hoke CHJ, 1997. New and improved vaccines for dengue, Japanese encephalitis, and yellow fever viruses. Levine MM, Woodrow GC, Kaper JB, Cobon GS, eds. New Generation Vaccines. New York: Marcel Dekker, 587–606.
  6. Halstead SB, Diwan AR, Marchette NJ, Palumbo NE, Srisukonth L, 1984. Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. I. Attributes of uncloned virus at different passage levels. Am J Trop Med Hyg 33 : 654–665.
  7. 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.
  8. Bhamarapravati N, Yoksan S, Chayaniyayothin T, Angsubphakorn S, Bunyaratvej A, 1987. 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 65 : 189–195.
  9. Eckels KH, Dubois DR, Putnak JR, 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 (suppl): (in press).
  10. Edelman R, Tacket CO, Wasserman SS, Vaughn DW, Eckels KH, Dubois DR, Summers PL, Hoke CH Jr, 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.
  11. Scott RM, Eckels KH, Bancroft WH, Summers PL, McCown JM, Anderson JH, Russell PK, 1983. Dengue 2 vaccine: dose response in volunteers in relation to yellow fever immune status. J Infect Dis 148 : 1055–1060.
  12. Eckels KH, Harrison VR, Summers PL, Russell PK, 1980. Dengue-2 vaccine: preparation from a small-plaque virus clone. Infect Immun 27 : 175–180.
  13. Innis BL, Eckels KH, Kraiselburd E, Dubois DR, Meadors GF, Gubler DJ, Burke DS, Bancroft WH, 1988. Virulence of a live dengue virus vaccine candidate: a possible new marker of dengue virus attenuation. J Infect Dis 158 : 876–880.
  14. Hoke CH Jr, Malinoski FJ, Eckels KH, Scott RM, Dubois DR, Summers PL, Simms T, Burrous J, Hasty SE, Bancroft WH, 1990. Preparation of an attenuated dengue 4 (341750 Carib) virus vaccine. II. Safety and immunogenicity in humans. Am J Trop Med Hyg 43 : 219–226.
  15. Bancroft WH, Top FH Jr, Eckels KH, Anderson JH Jr, McCown JM, Russell PK, 1981. Dengue-2 vaccine: virological, immunological, and clinical responses of six yellow fever-immune recipients. Infect Immun 31 : 698–703.
  16. Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, Puttisri P, Hoke CH Jr, 1989. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis cocirculate. Am J Trop Med Hyg 40 : 418–427.
  17. Clarke DH, Casals J, 1958. Techniques for hemagglutination and hemagglutination inhibition with arthropod-borne viruses. Am J Trop Med Hyg 7 : 561–573.
  18. Russell PK, Nisalak A, Sukhavachana P, Vivona S, 1967. A plaque reduction test for dengue virus neutralization antibodies. J Immunol 99 : 285–290.
  19. Putnak R, Barvir DA, Burrous JM, Dubois DR, D’Andrea VM, Hoke CH Jr, 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 : 1176–1184.
  20. McKee KT Jr, Bancroft WH, Eckels KH, Redfield RR, Summers PL, Russell PK, 1987. Lack of attenuation of a candidate dengue 1 vaccine (45AZ5) in human volunteers. Am J Trop Med Hyg 36 : 435–442.
  21. 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.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2003.69.17
Loading
/content/journals/10.4269/ajtmh.2003.69.17
Loading

Data & Media loading...

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