Development of a pentavalent vaccine against New World arenaviruses

Publication of the CIRI in the journal Nature Microbiology on January 5, 2023. Communication of the Institut Pasteur on January 6, 2023.

A team from the Institut Pasteur, hosted at CIRI, has developed and successfully tested on a primate model a pentavalent vaccine against the five pathogenic arenaviruses circulating in South America. Each of these viruses has a low incidence but a very high mortality rate, so combining them in a single vaccine would facilitate its development and protect the population as quickly as possible.

Pathogenic New World arenaviruses (NWAs) cause haemorrhagic fevers and can have high mortality rates, as shown in outbreaks in South America. Neutralizing antibodies (Abs) are critical for protection from NWAs. Having shown that the MOPEVAC vaccine, based on a hyperattenuated arenavirus, induces neutralizing Abs against Lassa fever, we hypothesized that expression of NWA glycoproteins in this platform might protect against NWAs. Cynomolgus monkeys immunized with MOPEVAC , targeting Machupo virus, prevented the lethality of this virus and induced partially NWA cross-reactive neutralizing Abs. We then developed the pentavalent MOPEVAC vaccine, expressing glycoproteins from all pathogenic South American NWAs. Immunization of cynomolgus monkeys with MOPEVAC induced neutralizing Abs 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. MOPEVAC may thus be efficient to protect against existing and potentially emerging NWAs.

Reference : A MOPEVAC multivalent vaccine induces sterile protection against New World arenaviruses in non-human primates . Stéphanie Reynard, Xavier Carnec, Caroline Picard, Virginie Borges-Cardoso, Alexandra Journeaux, Mathieu Mateo, Clara Germain, Jimmy Hortion, Laure Albrecht, Emeline Perthame, Natalia Pietrosemoli, Audrey Vallvé, Stéphane Barron, Aurélie Duthey, Orianne Lacroix, Ophélie Jourjon, Marie Moroso, Lyne Fellmann, Pierre-Henri Moreau, Maïlys Daniau, Catherine Legras-Lachuer, Manon Dirheimer, Caroline Carbonnelle, Hervé Raoul and Sylvain Baize. DOI: 10.1038/s41564’022 -01281-y

Image credits: Institut Pasteur/Unité Biologie des Infections Virales Emergentes (UBIVE) Laboratoire P4 Jean Mérieux Inserm US003