CPC A61K 38/162 (2013.01) [A61K 31/7048 (2013.01); A61K 31/713 (2013.01); A61K 39/12 (2013.01); C07K 14/005 (2013.01); C07K 14/1825 (2013.01); C07K 19/00 (2013.01); C12N 15/09 (2013.01); C12N 15/8613 (2013.01); A61K 2039/5254 (2013.01); A61K 2039/70 (2013.01); A61P 31/14 (2018.01); C07K 2319/00 (2013.01); C12N 2770/24122 (2013.01); C12N 2770/24134 (2013.01); C12N 2770/24141 (2013.01); C12N 2770/24143 (2013.01); C12N 2770/24162 (2013.01); Y02A 50/30 (2018.01)] | 30 Claims |
1. An immunogenic composition comprising a modified live, attenuated dengue-2 virus strain PDK-53, the immunogenic composition being a tetravalent composition, wherein the modified live, attenuated dengue-2 virus strain PDK-53
is encoded by a polynucleotide molecule encoding a modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule,
comprises an RNA transcribed from a cDNA comprising a polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule,
comprises one or more polypeptide molecules encoded by a polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule, or
is obtainable by a method for producing a modified live, attenuated dengue-2 virus strain PDK-53, the method comprising the following steps:
a) transcribing an RNA from a cDNA comprising a polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule, and
b) introducing the RNA transcribed in step a) into cells for production of the modified live, attenuated dengue-2 virus strain PDK-53,
wherein the polynucleotide molecule encoding the modified live, attenuated dengue-2 virus strain PDK-53 polypeptide molecule comprises at least one mutation, wherein one or more mutation is selected from the group consisting of:
an adenine to guanine mutation at position 592 in the numbering of SEQ ID NO: 14 encoding a glutamic acid instead of a lysine in the polypeptide molecule at amino acid position 166 in the numbering of SEQ ID NO: 6 corresponding to prM-52, and
an adenine to guanine mutation at position 8803 in the numbering of SEQ ID NO: 14 encoding a valine instead of an isoleucine in the polypeptide molecule at amino acid position 2903 in the numbering of SEQ ID NO: 6 corresponding to NS5-412, and comprising a dengue-1/dengue-2 chimera, wherein the dengue-1/dengue-2 chimera
comprises an adenine to guanine mutation at position 7311 in the numbering of SEO ID NO: 13.
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