Vaccine compositions for prevention against dengue virus infection
A technology of dengue virus, vaccine composition, applied in the direction of virus, vaccine, antiviral agent, etc.
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Embodiment 1
[0256] Example 1 : 1-year follow-up of patients vaccinated with a tetravalent dengue vaccine (TDV) composition comprising Chimerivax® DEN-1, DEN-2, DEN-3, and DEN-4 in Thailand
[0257] method
[0258] Study Design and Participants
[0259] Against virologically proven dengue disease, for the quadrivalent Chimerivax® vaccine (i.e. containing specific CYD-1 strains generated from the prM and E sequences of DEN1 PU0359 (TYP 1 140), generated from the prM and E sequences of DEN2 PUO218 Tetravalent of specific CYD-2 strains, specific CYD-3 strains generated from the prM and E sequences of DEN3 PaH881 / 88, and specific CYD-4 strains generated from the prM and E sequences of DEN4 1228 (TVP 980) Vaccine, see WO 03 / 101397 and Guy et al., Vaccine (2011), 29(42): 7229-41 ) A randomized controlled single center Phase IIb trial blinded to the observer was conducted. A total of 4002 schoolchildren aged 4-11 years in good health based on medical history and physical examination...
Embodiment 2
[0307] Example 2 : Identification of an optimized dengue vaccine strain for serotype 2
[0308] The purpose of this example is to identify dengue virus strains of serotype 2, which provide the basis for generating an optimized dengue vaccine composition against dengue virus of serotype 2, wherein when used in the method of the present invention, with Chimerivax® CYD- 2, the optimized dengue vaccine composition provides improved efficacy.
[0309] Criteria for optimal strain selection for determining the worldwide dengue 2 antigen include: (i) recently circulating strains; (ii) balanced selection between Asian and American strains; (iii) optimized strains should have such a prM-E sequence that is as similar as possible to the calculated global consensus sequence generated by alignment of available prM-E sequences of dengue virus of serotype 2; (iv) should Avoid predicting amino acid variations that affect antibody recognition; (v) rare amino acids at specific positions in ...
Embodiment 3
[0393] Example 3: Construction of cDNA clones corresponding to optimized serotype 2 chimeric viruses and production of encoded viruses
[0394] Basically following the teaching of Chambers et al. (1999, J. Virology 73(4): 3095-3101), Chimerivax® technology was used to realize the construction of chimeric dengue virus equivalent to the optimized serotype 2 strain. Reference is also made to international patent applications WO 98 / 37911, WO 03 / 101397, WO 07 / 021672, WO 08 / 007021, WO 08 / 047023 and WO 08 / 065315, which describe in detail the methods for constructing CYD-1, CYD2, CYD -3 and a similar approach for CYD-4. Briefly however, a chimeric dengue virus equivalent to an optimized serotype 2 strain was constructed as follows (note: the optimized chimeric dengue virus used YF strain YF17D204 (YF-VAX(R), Sanofi-Pasteur, Swiftwater, PA, USA ) genome backbone construction).
[0395] Construction of plasmid pSP1101
[0396] Construction of YF-VAX cDNA clone-pJSY2284....
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