The present application relates to Pichinde viruses with rearrangements of their open reading frames (ORF) in their genomes. In particular, described herein is a modified Pichinde virus genomic segment, wherein the Pichinde virus 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 Pichinde virus particles comprising one L segment and two S segments or two L segments and one S segment. The Pichinde virus, described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.

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.

Immunogens comprising a recombinant Lassa virus glycoprotein complex ectodomain trimer stabilized in a prefusion closed conformation, as well as methods of their use and production are disclosed. In several embodiments, the immunogen can be used to elicit an immune response to Lassa virus in a subject.

The present application relates to arenavirus particles containing a genome engineered such that an arenaviral open reading frame (ORF) is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. The arenavirus particles described herein are genetically stable and provide high-level transgene expression. In certain embodiments, the arenavirus particles are tri-segmented. In particular, described herein is a nucleotide sequence comprising one or more ORFs comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. Also described herein is an arenavirus particle containing a genome engineered such that an arenaviral ORF is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. Also described herein is an arenavirus genomic or antigenomic segment engineered such that the transcription thereof results in one or more mRNA transcripts comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. The arenavirus particles described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.

The present application provides immunotherapies for Hepatitis B virus infections. Provided herein are genetically modified arenaviral vectors suitable as vaccines for prevention and treatment of Hepatitis B virus infections. Also provided herein are pharmaceutical compositions and methods for the treatment of Hepatitis B virus infections. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of treating Hepatitis B virus infection.

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 chimeric polypeptides based on viral membrane fusion proteins. More particularly, the present invention discloses chimeric polypeptides that comprise a virion surface exposed portion of a viral fusion protein and a heterologous structure-stabilizing moiety, and to complexes of those chimeric polypeptides. The present invention also discloses the use of these complexes in compositions and methods for eliciting an immune response to a fusion protein of an enveloped virus, or complex of the fusion protein, and/or for treating or preventing an enveloped virus infection. The present invention further discloses the use of the heterologous structure-stabilizing moiety for oligomerizing heterologous molecules of interest.

The invention relates to a mutant of an arenavirus having improved antitumoral properties. The invention also relates to a method of generating such an arenavirus mutant, related pharmaceutical compositions, medical uses, methods of treatment, and isolated proteins and nucleic acids.

This invention relates to LY6G6F, VSIG10, TMEM25 and LSR proteins, which are suitable targets for immunotherapy, treatment of cancer, infectious disorders, and/or immune related disorders, and drug development. This invention further relates to soluble LY6G6F, VSIG10, TMEM25 and LSR molecules, extracellular domains of LY6G6F, VSIG10, TMEM25 and LSR and conjugates, which are suitable drugs for immunotherapy, treatment of cancer, infectious disorders, and/or immune related disorders. This invention further relates to antibodies and antigen binding fragments and conjugates containing same, and/or alternative scaffolds, specific for LY6G6F, VSIG10, TMEM25 or LSR molecules, which are suitable drugs for immunotherapy, treatment of cancer, infectious disorders, and/or immune related disorders.

The invention relates to recombinant VSV viruses and viral vectors which produce a glycoprotein GP of the lymphocyte choriomeningitis virus (LCMV) instead of the G protein of the VSV, to virus producing cells which produce LCMV-GP-pseudotyped VSV virions, and to the use of said vectors and cells in the therapy of solid tumors, especially brain tumors.