Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. IV. Characterization of a vaccine candidate in fetal rhesus lung cells
Halstead, S.B.; Eckels, K.H.; Putvatana, R.; Larsen, L.K.; Marchette, N.J.
American Journal of Tropical Medicine and Hygiene 33(4): 679-683
1984
ISSN/ISBN: 0002-9637 PMID: 6476215 Document Number: 224699
A strain of primary dog kidney (PDK)-passaged dengue (DEN) 4 (H-241) virus cloned by termnal dilution (PDK 35-TD3) was propagated in large volumes in fetal rhesus lung (FRhL) cells to proudce a candidate vaccine for evaluation in man. Production seed (FRhL p2) and candidate vaccine (FRhL p3) were subjected to rigorous safety tests to exclude contaminating microbial agents. There was no significant monkey neurovirulence of parental or PDK-passaged DEN-4 virus or of control fluid cultures. FRhL-passaged viruses retained the phenotypic characteristics; small (occasional medium) plaque; temperature sensitivity at 38.5.degree. C; and absence of plaque formation in African green monkey kidney cells, cytopathic effect in rhesus kidney LLC-MK2 cells, and viral growth in human monocytes. FRhL p2 virus displayed low virulence for monkeys; only 1 of 4 amimals was viremic and 3 of 4 developed low-titered antibody. FRhL p3 virus produced viremia in 3 monkeys and moderate to high hemagglutination-inhibition and neutralizing antibody titers in all animals. Virus at both passages in FRhL exhibited reduced neurovirulence in suckling mice as compared to parental DEN-4. Because of its safety and desirable monkey virulence attributes PDK 35-TD3 FRhL p3 is recommended for human phase I trial.