Compositions and methods of dengue virus chimeric constructs for use in vaccines
A kind of dengue fever virus, dengue fever technology, applied in the direction of drug combination, biochemical equipment and methods, virus, etc., can solve the problems of public health efforts such as difficulty in complete vaccine coverage
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Embodiment 1
[0109] In some exemplary methods, compositions for producing what are referred to herein as "master virus species (MVS)" are disclosed. These compositions may be derived from one or more live attenuated dengue viruses, such as DEN-1, DEN-2, DEN-3 and DEN-4. In certain methods, compositions may be derived from one or more live attenuated dengue viruses, including, but not limited to, the specific constructs disclosed herein referred to as DENVax-1, DENVax-2, DENVax-3, and DENVax-4 things. Among other exemplary methods, strategies for generating and characterizing these compositions are provided. In other embodiments, tetravalent dengue virus formulations and genetic and phenotypic characterization of these formulations are provided.
[0110] Production and analysis of pre-primary DENVax virus
[0111]Certain procedures are performed to generate pre-primary dengue species, such as a series of amplifications and purifications of dengue viruses (eg DENVax). First, P1 (passage ...
Embodiment 2
[0120] In some exemplary methods, compositions of master virus seeds, working virus seeds, and bulk virus seeds and their genetic and phenotypic characterizations are described. These compositions are provided for the manufacture of clinical material and eventual commercial vaccine supply. Continuous plaque purification and whole genome sequence analysis are incorporated into the manufacturing process to ensure that the composition of the vaccine species has optimal safety and genetic stability for the manufacture of clinical trial material.
[0121] Production and manufacturing quality control of MVS, WVS and BVS
[0122] In some studies, four DENVax MVS were generated by expansion of pre-primary P7 species in approved Vero cells. In other studies, MVS was used in cell culture to prepare large quantities of WVS. In addition, DENVax's BVS feedstock was expanded from WVS and formulated into a quadrivalent drug mixture for human clinical trials. Quality control of product rel...
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