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Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide and vaccination is one of the most effective ways to prevent disease. A suitable live-attenuated JEV vaccine could be formulated with a live-attenuated tetravalent dengue vaccine for the control of these viruses in endemic areas. Toward this goal, we generated chimeric virus vaccine candidates by replacing the precursor...
Mutations which increase the replication of dengue viruses in cell culture would greatly facilitate the manufacture of both a live attenuated or inactivated dengue virus vaccine. We have identified eight missense mutations in dengue virus type 4 (DEN4) that increase the plaque size and kinetics of replication of recombinant DEN4 virus in Vero cells. DEN4 viruses bearing these Vero cell adaptation...
Mutations that restrict replication of dengue virus have been sought for the generation of recombinant live-attenuated dengue virus vaccines. Dengue virus type 4 (DEN4) was previously grown in Vero cells in the presence of 5-fluorouracil, and the characterization of 1248 mutagenized, Vero cell passaged clones identified 20 temperature-sensitive (ts) mutant viruses that were attenuated (att) in suckling...
A recombinant human antibody fragment, designated RSV Fab 19, efficiently neutralizes respiratory syncytial virus (RSV). Here we report the results of our sequence analysis of antibody escape mutants that identified F glycoprotein amino acids critical for binding of human or murine RSV F-neutralizing antibodies.
Respiratory syncytial virus (RSV)cpts248/404 is a live-attenuated, temperature-sensitive (ts) vaccine candidate derived from cold-passagedcpRSV by two rounds of chemical mutagenesis and biological selection. Previous sequence analysis showed that these two steps introduced three single nucleotide substitutions into thecpRSV parent. Two of these occurred within the coding sequence for the L protein,...
The complete nucleotide sequence of the RSVcpts-248/404 live attenuated vaccine candidate was determined from cloned cDNA and was compared to that of the RSV A2/HEK7 wild-type, cold-passagedcp-RSV, andcpts-248 virus, which constitute the series of progenitor viruses. RSVcpts-248/404 is more attenuated and more temperature sensitive (ts) (shut-off temperature 36°) than itscpts-248 parent virus (shut-off...
In previous studies, a mutant (cp-RSV) of the RSV A2 strain derived from 52 serial cold passages in bovine embryonic tissue culture was highly attenuated in seropositive adults and children but caused upper respiratory tract disease in seronegative infants. We investigated the genetic basis for this attenuation phenotype by comparing the complete genomic RNA sequence of this virus with the published...
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