US 12,070,494 B2
Chimeric flavivirus lyssavirus vaccines
Kai Dallmeier, Kessel-Lo (BE); Niraj Mishra, Leuven (BE); Johan Neyts, Kessel-Lo (BE); and Lorena Sanchez, Wijgmaal (BE)
Assigned to KATHOLIEKE UNIVERSITEIT LEUVEN, Leuven (BE)
Appl. No. 17/273,985
Filed by KATHOLIEKE UNIVERSITEIT LEUVEN, Leuven (BE)
PCT Filed Sep. 6, 2019, PCT No. PCT/EP2019/073897
§ 371(c)(1), (2) Date Mar. 5, 2021,
PCT Pub. No. WO2020/049175, PCT Pub. Date Mar. 12, 2020.
Claims priority of application No. 1814563 (GB), filed on Sep. 7, 2018.
Prior Publication US 2021/0353735 A1, Nov. 18, 2021
Int. Cl. A61K 39/12 (2006.01); A61K 39/00 (2006.01); C12N 7/00 (2006.01); C12N 15/85 (2006.01)
CPC A61K 39/12 (2013.01) [C12N 7/00 (2013.01); C12N 15/85 (2013.01); A61K 2039/5254 (2013.01); C12N 2760/20134 (2013.01); C12N 2770/24134 (2013.01); C12N 2800/204 (2013.01); C12N 2820/002 (2013.01)] 23 Claims
 
1. A polynucleotide comprising a sequence of a live, infectious, attenuated Flavivirus wherein a nucleotide sequence encoding at least a part of a Lyssavirus G protein sequence is located at the intergenic region between an E gene and an NS1 gene of the Flavivirus, such that a chimeric virus is expressed, wherein the encoded sequence is located C terminally of an E protein of the Flavivirus and N terminally of a signal peptide of an NS1 protein of the Flavivirus, and wherein the encoded sequence comprises in the following order:
(1) a further signal peptide of a Flavivirus NS1 protein,
(2) a lyssavirus G protein lacking a functional signal peptide, comprising an IIb epitope, comprising a C terminal TM membrane, and comprising a C terminal cytoplasmatic sequence, and
(3) a TM2 domain of a flaviviral E protein.