View/Open - TWAS & OWSD Thesis Repository Home

.'trials in children are planned for 2002-2003. This vaccine is licensed toGlaxosrnithkline, Rixensart, Belgium (Halstead and Deen, 2002).2.6.2. WEST NILE VIRUS VACCINE IN PROGRESS.There is currently no vaccine against WNV..However, a formalininactivatedmouse brain vaccine against the closely related JEV [JE-VAX(R)Aventis- Pasteur] is marketed in the US for travelers (Monath et al., 2001).Immunity to JEV may provide a degree of cross-protection in animals (Govemdhanet al., 1992), but there are insufficient data to warrant a recommendation for"Jennerian" of humans and horses (Monath et. al.. 2001). The safety of JE vaccinein the prevention of West Nile disease has not been established, and studies in micesuggest that heterologous immunity could potentiate brain inflammation followingneuroinvasion by WNV (Broom et al., 2000). Immunization of birds with JE­VAX(R) did not provide a high level of protection against WNV challenge (Monathet. al., 2001).2.6.2.1 DEVELOPMENT OF CIIIMERI Vax -WN as described byMonath et al., (2001)Genes encoding two proteins [prM and E] of YF 17D vaccine virus werereplaced with the corresponding genes of WNV. The resulting virion has theenvelope of WNV, containing structures involved in virus-cell attachment and virusintemalization, all antigenic determinants for neutralization, and epitope (s) forcytotoxic T Iymphocytes. The nucleocapsid (C) protein, nonstructural proteins andnon-translated termini responsible for virus replication remain those of the originalYF l7D virus. The chimeric virus should thus replicate efficiently in the host butimmunize against the heterologous (West Nile) virus (Monath et, al., 2001).The construction of a chimeric YF 17DI WNV was performed by thereversed Transcription of viral RNA to c DNA, which was then cloned in a twoplasmidsystem. The donor prM-E genes from wild typel999 strain of WNV wereusedfor the construction (Monath et. aI., 2001). That report also stated that, Plasmidencoding virus genomic sequences were propagated .in E coli. Appropriaterestriction sites were introduced to allow excision and in vitro ligation of plasmidfragments to produce full- length DNA template. Transcription of the linear DNA55