The present application relates to arenaviruses with rearrangements of their open reading frames (“ORF”) in their genomes. In particular, described herein is a modified arenavirus genomic segment, wherein the arenavirus genomic segment is engineered to carry a viral ORF in a position other than the wild-type position of the ORF. Also described herein are trisegmented arenavirus particles comprising one L segment and two S segments or two L segments and one S segment. The arenavirus, described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.

A recombinant attenuated Mopeia virus (MOPV) comprising a recombinant genomic S segment that encodes a nucleoprotein having attenuated exonuclease activity, and optionally further encodes a non-MOPV arenavirus glycoprotein. Use of the recombinant attenuated MOPV to induce an immune response in a subject.

A recombinant attenuated Mopeia virus (MOPV) comprising a recombinant genomic S segment that encodes a nucleoprotein having attenuated exonuclease activity, and optionally further encodes a non-MOPV arenavirus glycoprotein. Use of the recombinant attenuated MOPV to induce an immune response in a subject.

The present application relates to arenaviruses with rearrangements of their open reading frames (“ORF”) in their genomes. In particular, described herein is a modified arenavirus genomic segment, wherein the arenavirus genomic segment is engineered to carry a viral ORF in a position other than the wild-type position of the ORF. Also described herein are trisegmented arenavirus particles comprising one L segment and two S segments or two L segments and one S segment. The arenavirus, described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.

The present application relates to arenaviruses with rearrangements of their open reading frames (ORF) in their genomes. In particular, described herein is a modified arenavirus genomic segment, wherein the arenavirus genomic segment is engineered to carry a viral ORF in a position other than the wild-type position of the ORF. Also described herein are trisegmented arenavirus particles comprising one L segment and two S segments or two L segments and one S segment. The arenavirus, described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.

A recombinant attenuated Mopeia virus (MOPV) comprising a recombinant genomic S segment that encodes a nucleoprotein having attenuated exonuclease activity, and optionally further encodes a non-MOPV arenavirus glycoprotein. Use of the recombinant attenuated MOPV to induce an immune response in a subject.

Disclosed are compositions and methods related to recombinant arenaviruses and their use in vaccines for the treatment or prevention of an arenavirus infection.

The invention relates to genetically modified arenaviruses suitable for the treatment of neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable for treatment of neoplastic diseases and/or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding one or more antigenic fragment(s) of mutant KRAS alone or to further include a nucleotide sequence encoding one or more antigenic fragment(s) of a mutated cancer driver gene (e.g., a mutant TP53) or a tumor-associated antigen.

The present disclosure relates to a novel live-attenuated Junn virus (JUNV), which exhibits reduced likelihood for virulence reversion compared to the Candid#1 vaccine strain. The live-attenuated JUNV comprises at least three mutations in its GPC protein compared to a pathogenic strain of JUNV. One mutation is a substitution mutation at residue 427 like the Candid#1 vaccine strain. The live-attenuated JUNV comprises at least one mutation altering a NxT/S glycosylation motif in a region spanning residues 150-175 of the Junn virus GPC protein to inactivate the glycosylation site. In some embodiments, the live-attenuated JUNV further comprises a substitution mutation at residue 33. Compositions comprising the variant JUNV and methods of using the JUNV and compositions are also described herein.