Substitution of Wild‐Type Yellow Fever Asibi Sequences for 17D Vaccine Sequencesin ChimeriVax–Dengue 4 Does Not Enhance Infection of Aedes aegypti Mosquitoes
1Department of Pathology, University of Texas Medical Branch, Galveston; 2Sanofi Pasteur, Global Research and Development, Campus Mérieux, Marcy‐L’Etoile, France
To address concerns that a flavivirus vaccine/wild‐type recombinant virus might have a high mosquito infectivity phenotype, the yellow fever virus (YFV) 17D backbone of the ChimeriVax–dengue 4 virus was replaced with the corresponding gene sequences of the virulent YFV Asibi strain. Field‐collected and laboratory‐colonized Aedes aegypti mosquitoes were fed on blood containing each of the viruses under investigation and held for 14 days after infection. Infection and dissemination rates were based on antigen detection in titrated body or head triturates. Our data indicate that, even in the highly unlikely event of recombination or substantial backbone reversion, virulent sequences do not enhance the transmissibility of ChimeriVax viruses. In light of the low‐level viremias that have been observed after vaccination in human volunteers coupled with low mosquito infectivity, it is predicted that the risk of mosquito infection and transmission of ChimeriVax vaccine recombinant/revertant viruses in nature is minimal.
Received 19 August 2007; accepted 17 September 2007; electronically published 11 February 2008.
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(See the brief report by McGee et al., on pages 693–7.)
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Online publication date: 1-Sep-2008.
Online publication date: 1-Mar-2008.
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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. C.E.M., K.T, D.L.V., K.L.M., and S.H. do not have any financial interest in Sanofi‐Pasteur.
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.); National Institutes of Health (grant T32 A107536 to D.L.V.).