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1 March 2008

Volume 197, Number 5
The Journal of Infectious Diseases 2008;197:693–697
© 2008 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2008/19705-0013$15.00
DOI: 10.1086/527329
BRIEF REPORT

Recombinant Chimeric Virus with Wild‐Type Dengue 4 Virus Premembrane and Envelope and Virulent Yellow Fever Virus Asibi Backbone Sequences Is Dramatically Attenuated in Nonhuman Primates

Charles E. McGee,1

Mark G. Lewis,2

Marisa St. Claire,2

Wendeline Wagner,2

Jean Lang,3

Bruno Guy,3

Konstantin Tsetsarkin,1

Stephen Higgs,1 and

Thierry Decelle3

1Department of Pathology, University of Texas Medical Branch, Galveston; 2BioQual, Rockville, Maryland; 3Sanofi Pasteur, Global Research and Development, Campus Mérieux, Marcy‐L’Etoile, France

Candidate vaccine ChimeriVax viruses are attenuated, efficacious, safe, and highly unlikely to be transmitted by arthropod vectors. Nevertheless, concerns have been raised about the use of these vaccines because of the potential for recombination between vaccine and wild‐type (WT) strains. To evaluate the vertebrate pathogenicity of such a worst‐case recombinant, ChimeriVax–dengue (DEN) 4 virus was chimerized with the WT Asibi yellow fever virus. In this worst‐case scenario, chimeric viruses remained fully attenuated in nonhuman primates. We therefore conclude that, even in the highly unlikely event of “virulent” backbone reversion, the safety of ChimeriVax‐DEN vaccines would not be compromised.

Received 19 July 2007; accepted 19 September 2007; electronically published 11 February 2008.

Reprints or correspondence: Charles McGee, University of Texas Medical Branch, Dept. of Pathology, 301 University Blvd., Galveston, TX 77555‐0609 ().

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  • Potential conflicts of interest: Sanofi‐Pasteur, manufacturer of the ChimeriVax vaccine, sponsored this study financially. J.L., B.G., and T.D. are all current employees of Sanofi‐Pasteur and have a financial interest in this company, which may include stock ownership.

    Financial support: Sanofi‐Pasteur; Centers for Disease Control and Prevention Fellowship Training Program in Vector‐Borne Infectious Diseases (grant T01/CCT622892 to C.E.M.).

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