Format

Send to

Choose Destination
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.

Author information

1
Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France.
2
Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS UMR5308, Lyon, France.
3
ViroScan3D SAS, Trévoux, France.
4
Bioinformatics and Biostatistics Hub-Department of Computational Biology, USR 3756 CNRS, Institut Pasteur, Paris, France.
5
Laboratoire P4 INSERM-Jean Mérieux, INSERM US003, Lyon, France.
6
SILABE, Université de Strasbourg, Fort Foch, Niederhausbergen, France.
7
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.
8
Viral Genomics and Vaccination, Institut Pasteur, CNRS UMR-3569, Paris, France.
9
Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France. sylvain.baize@pasteur.fr.

Abstract

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.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center