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Sci Transl Med. 2019 Oct 2;11(512). pii: eaaw3163. doi: 10.1126/scitranslmed.aaw3163.

Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot.

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Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France.
Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS UMR5308, Lyon, France.
ViroScan3D SAS, Trévoux, France.
Bioinformatics and Biostatistics Hub-Department of Computational Biology, USR 3756 CNRS, Institut Pasteur, Paris, France.
Laboratoire P4 INSERM-Jean Mérieux, INSERM US003, Lyon, France.
SILABE, Université de Strasbourg, Fort Foch, Niederhausbergen, France.
Laboratoire Innovations Technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Commissariat à l'Energie Atomique, Bagnols-sur-Cèze, France.
Viral Genomics and Vaccination, Institut Pasteur, CNRS UMR-3569, Paris, France.
Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France.


Lassa fever is a major threat in Western Africa. The large number of people living at risk for this disease calls for the development of a vaccine against Lassa virus (LASV). We generated live-attenuated LASV vaccines based on measles virus and Mopeia virus platforms and expressing different LASV antigens, with the aim to develop a vaccine able to protect after a single shot. We compared the efficacy of these vaccines against LASV in cynomolgus monkeys. The vaccines were well tolerated and protected the animals from LASV infection and disease after a single immunization but with varying efficacy. Analysis of the immune responses showed that complete protection was associated with robust secondary T cell and antibody responses against LASV. Transcriptomic and proteomic analyses showed an early activation of innate immunity and T cell priming after immunization with the most effective vaccines, with changes detectable as early as 2 days after immunization. The most efficacious vaccine candidate, a measles vector simultaneously expressing LASV glycoprotein and nucleoprotein, has been selected for further clinical evaluation.

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