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A single-shot Lassa vaccine induces long-term immunity and protects cynomolgus monkeys against heterologous strains
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Edité par CCSD ; American Association for the Advancement of Science (AAAS) -
Acknowledgments: We thank P. Regnard (Silabe, Strasbourg) for medical care given to the monkeys. We thank S. Mundweiller, S. Godard, E. Moissonnier, D. Thomas, S. Mély, B. Labrosse, D. Pannetier, and C. Léculier (P4 INSERM–Jean Mérieux, US003, INSERM) for assistance in conducting the BSL-4 experiments. We are grateful to G. Fourcaud and B. Lafoux (Institut Pasteur, CIRI, Lyon) for technical help with histological studies. We thank S. Becker for providing us with the Josiah strain and T. G. Ksiasek, P. E. Rollin, and P. Jahrling for the LASV monoclonal antibodies. We also thank L. Branco (Zalgen Labs) for providing recombinant proteins. We are grateful to THEMIS Bioscience GmbH, a wholly owned subsidiary of Merck & Co. Inc. (E. Tauber, A. Kort, K. Ramsauer, S. Schrauf, Y. Tomberger, and R. Tschismarov), to the Coalition for Epidemic Preparedness and Innovations (R. Hatchett, G. Thiry, and M. Saville), and to C. Gerke (Department of Innovation Development, Institut Pasteur) for invaluable support. International audience. A safe and protective Lassa virus vaccine is crucially needed in Western Africa to stem the recurrent outbreaks of Lassa virus infections in Nigeria and the emergence of Lassa virus in previously unaffected countries, such as Benin and Togo. Major challenges in developing a Lassa virus vaccine include the high diversity of circulating strains and their reemergence from 1 year to another. To address each of these challenges, we immunized cynomolgus monkeys with a measles virus vector expressing the Lassa virus glycoprotein and nucleoprotein of the prototypic Lassa virus strain Josiah (MeV-NP). To evaluate vaccine efficacy against heterologous strains of Lassa virus, we challenged the monkeys a month later with heterologous strains from lineage II or lineage VII, finding that the vaccine was protective against these strains. A second cohort of monkeys was challenged 1 year later with the homologous Josiah strain, finding that a single dose of MeV-NP was sufficient to protect all vaccinated monkeys. These studies demonstrate that MeV-NP can generate both long-lasting immune responses and responses that are able to protect against diverse strains of Lassa virus.
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