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Construction and characterization of a second-generation pseudoinfectious West Nile virus vaccine propagated using a new cultivation system |
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| Authors: | Widman Douglas G Ishikawa Tomohiro Fayzulin Rafik Bourne Nigel Mason Peter W |
| Affiliation: | aDepartment of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA bDepartment of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA cSealy Center for Vaccine Development, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA dDepartment of Pediatrics, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA |
| Abstract: | Safer vaccines are needed to prevent flavivirus diseases. To help develop these products we have produced a pseudoinfectious West Nile virus (WNV) lacking a functional C gene which we have named RepliVAX WN. Here we demonstrate that RepliVAX WN can be safely propagated at high titer in BHK cells and vaccine-certified Vero cells engineered to stably express the C protein needed to trans-complement RepliVAX WN growth. Using these BHK cells we selected a better growing mutant RepliVAX WN population and used this to generate a second-generation RepliVAX WN (RepliVAX WN.2). RepliVAX WN.2 grown in these C-expressing cell lines safely elicit strong protective immunity against WNV disease in mice and hamsters. Taken together, these results indicate the clinical utility of RepliVAX WN.2 as a vaccine candidate against West Nile encephalitis. |
| Keywords: | West Nile virus Single-cycle virus Subviral particles |
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