Sci Transl Med. 2019 Oct 2;11(512). pii: eaaw3163. PMID: 31578242
Mateo M, Reynard S, Carnec X, Journeaux A, Baillet N, Schaeffer J, Picard C, Legras-Lachuer C, Allan R, Perthame E, Hillion KH, Pietrosemoli N, Dillies MA, Barrot L, Vallve A, Barron S, Fellmann L, Gaillard JC, Armengaud J, Carbonnelle C, Raoul H, Tangy F, Baize S
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.