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ChimeriVaxTM-dengue (DEN) viruses are live attenuated vaccine candidates. They are constructed by replacing the premembrane (prM) and envelope (E) genes of the yellow fever (YF) 17D virus vaccine with the corresponding genes from wild-type DEN viruses (serotypes 1–4) isolated from humans. In this study, the growth kinetics of ChimeriVaxTM-DEN1-4 and parent viruses (wild-type DEN-1-4 and YF 17D) were assessed in human myeloid dendritic cells (DCs) and in three hepatic cell lines (HepG2, Huh7, and THLE-3). In DC, ChimeriVaxTM-DEN-1-4 showed similar growth kinetics to their parent viruses, wild-type DEN virus (propagated in Vero cells), or YF 17D virus (peak titers ~3–4.5 log10 plaque-forming units (PFU)/mL at 48–72 hours post-infection). Parent wild-type DEN-1-4 viruses derived from C6/36 mosquito cells did not show any growth at a multiplicity of infection of 0.1 in DCs, except for DEN-2 virus, which grew to a modest titer of 2.5 log10 PFU/mL at 48 hours post-infection. ChimeriVaxTM-DEN1-4 grew to significantly lower titers (2–5 log10 PFU/mL) than YF 17D virus in hepatic cell lines THLE-3 and HepG2, but not in Huh7 cells. These experiments suggest that ChimeriVaxTM-DEN1-4 viruses replicate similarly to YF-VAX® in DCs, but at a lower level than YF 17D virus in hepatic cell lines. The lack of growth of chimeric viruses in human hepatic cells suggests that these viruses may be less hepatotropic than YF 17D virus vaccine in humans.
Received March 16, 2004. Accepted for publication August 6, 2004.
Acknowledgments: We thank P. Papastathis (Acambis, Inc.) for excellent technical assistance and cell culture support.
Financial support: This work was supported by Aventis Pasteur (Marcy-L’Etoile, France).
Disclosure: Farshad Guirakhoo holds stock of Acambis, Inc. and is currently conducting research sponsored by this company. This statement is made in the interest of full disclosure and not because the author considers this to be a conflict of interest.
Authors’ addresses: Samantha Brandler, Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria. Nathan Brown, Thomas H. Ermak, Fred Mitchell, Megan Parsons, Zhenxi Zhang, Thomas P. Monath, and Farshad Guirakhoo, Acambis, Inc., 38 Sidney Street, Cambridge, MA 02139, Telephone: 617–761–4323, Fax: 617–494–1741, E-mail: farshad.guirakhoo{at}acambis.com. Jean Lang, Aventis Pasteur, Campus Merieux, 1541 Avenue Marcel Merieux, Marcy-L’Etoile F-69280, France.
Reprint requests: Farshad Guirakhoo, Acambis, Inc., 38 Sidney Street, Cambridge, MA 02139.
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