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1. (WO2018129160) LIVE ATTENUATED FLAVIVIRUS VACCINES AND METHODS OF USING AND MAKING SAME

Pub. No.:    WO/2018/129160    International Application No.:    PCT/US2018/012346
Publication Date: Fri Jul 13 01:59:59 CEST 2018 International Filing Date: Fri Jan 05 00:59:59 CET 2018
IPC: A61K 39/12
C12N 7/04
C12N 15/11
C12N 15/113
C12N 15/86
Applicants: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Inventors: PLETNEV, Alexander, G.
TSETSARKIN, Konstantin, A.
Title: LIVE ATTENUATED FLAVIVIRUS VACCINES AND METHODS OF USING AND MAKING SAME
Abstract:
Recombinant flaviviruses and flavivirus genomes which have been attenuated by using a dual approach involving (a) the insertion of miRNA targeting sequences and (b) insertion of an internal ribosome entry site (IRES) upstream of a viral protein, thereby forming a bicistronic virus construct, causing manipulation of the level or amount of virus protein(s) under translational control of the IRES as a separate cistronic element are provided. Recombinant flaviviruses and flavivirus genomes that have been attenuated by an approach involving insertion of an IRES upstream of a viral protein and altering the arrangement of flavivirus protein genes in the genome are also disclosed. Methods for constructing such attenuated flaviviruses, immunogenic compositions comprising same, and methods for inducing an immune response against a flavivirus by administering an effective amount of compositions comprising the attenuated flaviviruses are also provided.