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