The MOPEVAC multivalent vaccine induces sterile protection against New World Arenaviruses in non-human primates

Pathogenic New World arenaviruses (NWAs) cause hemorrhagic fevers and can have high mortality rates, as shown in recent outbreaks in South America. Neutralizing antibodies (Nabs) are critical for protection from NWAs. Having shown that the MOPEVAC vaccine, based on a hyper-attenuated arenavirus, induces NAbs against Lassa fever, we hypothesized that expression of NWA glycoproteins in this platform might protect against NWAs. Cynomolgus monkeys immunized with MOPEVACMAC, targeting Machupo virus, prevented the lethality of this virus and induced partially NWA-cross-reactive Nabs. We then developed the pentavalent MOPEVACNEW vaccine, expressing glycoproteins from all pathogenic South American NWAs. Immunization of cynomolgus monkeys with MOPEVACNEW induced Nabs against five NWAs, strong innate followed by adaptive immune responses as detected by transcriptomics, and provided sterile protection against Machupo virus and the genetically distant Guanarito virus. MOPEVACNEW may thus be efficient to protect against existing and, potentially, emerging NWAs."counts_pre.txt" and "target_pre.txt" stands for "pre infection" and "counts_post.txt" and "target_post.txt" stands for "post infection". Methods for obtaining the count table = Bioinformatics analysis was performed using the RNA-seq pipeline from Sequana. Reads were cleaned of adapter sequences and low-quality sequences using cutadapt version 1.11. Only sequences of at least 25 nucleotides in length were considered for further analysis. STAR version 2.5.0a, with default parameters, was used for alignment against the reference genome (Macaca Fascicularis 5 from ENSEMBL version 95). Reads were assigned to genes using featureCounts version 1.4.6-p3 from the Subreads package (parameters: -t gene -g ID -O -s 2). Cokelaer et al, (2017), 'Sequana': a Set of Snakemake NGS pipelines, Journal of Open Source Software, 2(16), 352, doi:10.21105/joss.00352 Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal; Vol 17, No 1 Next Gener. Seq. Data Anal. - 10.14806/ej.17.1.200 (2011). Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013). Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014