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1. (WO2017156146) MODIFIED ARENAVIRUS

Pub. No.:    WO/2017/156146    International Application No.:    PCT/US2017/021390
Publication Date: Fri Sep 15 01:59:59 CEST 2017 International Filing Date: Thu Mar 09 00:59:59 CET 2017
IPC: A61K 39/12
A61P 37/04
Applicants: UNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGE
Inventors: BRUCE, Emily Adaline
BOTTEN, Jason William
ZIEGLER, Christopher Michael
Title: MODIFIED ARENAVIRUS
Abstract:
Provided are modified arenaviruses and populations thereof, wherein the modified arenaviruses include i) an introduced PPXY domain; ii) an increased number of PPXY domains; iii) a substituted amino acid in place of S41 in a viral Z protein that is not a substrate for a serine or tyrosine kinase, or a combination of i)-iii). A PPXY domain can include a phosphomimetic replacement of the Y amino acid. Modified Old World and New World arenaviruses are included. Arenavirus production is provided using cell cultures that contain a kinase inhibitor that inhibits a kinase that can phosphorylate the Y amino acid of the PPXY domain, or by cells that have disrupted kinase gene expression, or by cells that have a disrupted ESCRT system. Also provided are pharmaceutical formulations that contain modified arenaviruses, and methods of using such formulations for stimulating an immune response hat is fully or partially protective against arenavirus infection. Also provided is a method for producing a population of arenaviruses that involves culturing cells that i) are infected with a wild type arenavirus, or ii) comprise one or more expression vectors encoding the arenavirus, wherein the cells are characterized by at least one of: a) comprising kinase inhibitor; or b) a modification such that expression of a kinase capable of phosphorylating a tyrosine in a PPXY domain of the arenavirus is inhibited or eliminated, or c) a disrupted ESCRT pathway.