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Four chimeric yellow fever (YF) 17D-dengue (DEN) candidate vaccine viruses (ChimeriVaxTM-DEN; Acambis, Cambridge, MA) were characterized in Aedes aegypti and Ae. albopictus mosquitoes collected from Thailand. The four vaccine viruses contained the relevant prM and E genes of wild-type dengue viruses (DENV; serotypes 1–4) substituted for the equivalent genes in the YF vaccine virus (17D) backbone. Each chimera conferred protection against the homologous DENV serotype; a tetravalent mix of all four chimeras stimulates an immune response against all serotypes. Field-collected mosquitoes from Thailand were fed on blood containing each of the viruses under study and held 21 days after infection. Infection and dissemination rates were based on antigen detection in the body or head tissues, respectively. All four wild-type DENV serotypes infected and disseminated, but the candidate vaccine viruses were highly attenuated in mosquitoes with respect to infection and especially with respect to dissemination. Considering the low level viremias anticipated in humans vaccinated with these viruses, it is predicted that the risks of infection and transmission by mosquitoes in nature is minimal.
Received May 1, 2006. Accepted for publication June 21, 2006.
Acknowledgments: The authors thank J. Huang for assistance in rearing mosquitoes.
Financial support: This work was supported by Sanofi-Pasteur, Marcy-L’Etoile, France. Kate McElroy and Charles McGee are recipients of CDC Fellowships for training in vector-borne infectious diseases (TO1/CCT622892).
Disclosure: Some of the authors wish to disclose that they have financial interest in Acambis, the company that sponsored the study. Some authors are current or former employees of Acambis. These statements are being made in the interest of full disclosure and not because the authors consider this to be a conflict of interest.
* Address correspondence to Stephen Higgs, Department of Pathology, Keiller 2.104 301 University Boulevard, Galveston, TX 77555-0609. E-mail: sthiggs{at}utmb.edu
Authors’ addresses: Stephen Higgs, Dana Vanlandingham, Kimberly Klingler, Kate McElroy, and Charles E. McGee, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609. Laura Harrington, Department of Entomology, 3138 Comstock Hall, Cornell University, Ithaca, NY 14853. Jean Lang, Sanofi Pasteur, Campus Mérieux, 1541 Avenue Marcel Mérieux, Marcy-L’étoile F-69280, France. Thomas Monath and Farshad Guirakhoo, Acambis, Inc., 38 Sidney Street, Cambridge, MA 02139, Telephone: 617-761-4323, Fax: 617-494-1741. Current address for Thomas Monath, Kleiner Perkins Caufield & Byers, 21 Finn Road, Harvard MA 01451. Farshad Guirakhoo, Acambis, Inc., 38 Sidney Street, Cambridge, MA 02139, Telephone
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