Multivalent mopevac-based immunogenic composition for vaccination against new world arenaviruses and therapeutic use(s) thereof

A method of preparing a recombinant live attenuated Mopeia virus (MOPV) in a eukaryotic host cell, said recombinant live attenuated Mopeia virus (MOPV) comprising an heterologous nucleic acid encoding a New World arenavirus GPC from an arenavirus selected among:

• Machupo virus (MACV), Sabia virus (SABV), Chapare virus (CHAPV), Junin virus (JUNV) and Guanarito virus (GTOV), wherein the method comprises the steps of:
• transfecting the eukaryotic host cell with plasmids wherein:
• a first plasmid that comprises a polynucleotide which is an expression cassette encoding the L segment antigenomic transcript of a Mopeia vRNA (L vRNA segment expression cassette);
• a second plasmid that comprises a polynucleotide which is an expression cassette encoding a chimeric S segment antigenomic transcript of a Mopeia vRNA, in particular a S segment that is deleted for the ORF of the glycoprotein precursor (GPC) of the Mopeia virus, wherein the polynucleotide comprises (i) the ORF of the GPC protein of a New World arenavirus selected among:
• Machupo virus (MACV), Sabia virus (SABV), Chapare virus (CHAPV), Junin virus (JUNV) and Guanarito virus (GTOV), and (ii) the ORF of a nucleoprotein (NP) protein which is mutated by amino acid residue substitution(s) in the wild type NP of the Mopeia virus to have attenuated exonuclease activity;
• an expression cassette for the L protein of the Mopeia virus wherein said cassette is either present as an insert in the second plasmid or is contained in a third plasmid;
• an expression cassette for the NP protein of the Mopeia virus wherein said cassette is either as an insert in the first plasmid or is contained in fourth plasmid;
• allowing ribonucleoproteins of the recombinant Mopeia virus to form and expression of the New world arenavirus GPC gene to assemble into recombinant live attenuated viral particles and;
• recovering recombinant live attenuated Mopeia virus expressing the GPC of a New World arenavirus selected among:
• Machupo virus (MACV), Sabia virus (SABV), Chapare virus (CHAPV), Junin virus (JUNV) and Guanarito virus (GTOV).