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Am. J. Trop. Med. Hyg., 43(2), 1990, pp. 212-218
Copyright © 1990 by The American Society of Tropical Medicine and Hygiene

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Preparation of an Attenuated Dengue 4 (341750 Carib) Virus Vaccine

I. Pre-Clinical Studies

Nyven J. Marchette, Doria R. Dubois, Linda K. Larsen, Peter L. Summers, Edmundo G. Kraiselburd, Duane J. Gubler AND Kenneth H. Eckels
University of Hawaii, Honolulu, Hawaii; Walter Reed Army Institute of Research, Washington, DC; University of Puerto Rico, San Juan, Puerto Rico; Center for Disease Control, San Juan Laboratories, San Juan, Puerto Rico

Dengue 4 (DEN-4) virus strain 341750 Carib was modified by serial passage in primary canine kidney (PCK) cell cultures. By the 15th PCK passage, this virus was less infectious for monkeys and resulted in a significantly reduced viremia as compared to the parent DEN-4 virus. The 30th PCK passage of DEN-4 341750 Carib was non-infectious for monkeys. A vaccine prepared at the 20th PCK passage in DBS-FRhL-2 cells stimulated the production of both neutralizing and hemagglutination inhibition antibodies in monkeys; these animals were also protected against challenge with the homologous strain as well as a heterologous strain of DEN-4. An ID50 titration in monkeys resulted in a titer of > 104 plaque-forming units (PFU) for the vaccine virus and 0.5 PFU for the parent virus. Reduced monkey infectivity of this magnitude has been correlated with human attenuation in previous dengue vaccine candidates. The DEN-4 strain 341750 Carib PCK-20/FRhL-4 vaccine has been characterized and sufficiently tested to be considered for safety and immunogenicity trials in humans.




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C.-J. Lai, A. P. Goncalvez, R. Men, C. Wernly, O. Donau, R. E. Engle, and R. H. Purcell
Epitope Determinants of a Chimpanzee Dengue Virus Type 4 (DENV-4)-Neutralizing Antibody and Protection against DENV-4 Challenge in Mice and Rhesus Monkeys by Passively Transferred Humanized Antibody
J. Virol., December 1, 2007; 81(23): 12766 - 12774.
[Abstract] [Full Text] [PDF]


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Copyright © 1990 by the American Society of Tropical Medicine and Hygiene.