Balanced immunity to Lassa virus glycoprotein and nucleoprotein is associated with full protection of macaques after a single shot of different vaccines

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 compared the efficacy of measles-based and Mopeia-based vaccine platforms against LASV in cynomolgus monkeys. The vaccines were well tolerated and protected the animals from Lassa virus infection and disease after a single immunization but with different efficacy. Analyses of immune responses demonstrated that complete protection was associated with early and robust T-cell responses against LASV but not humoral responses nor neutralizing antibodies. Transcriptomic and proteomic analyses performed during the immunization phase confirmed the role of early innate immunity and T-cell priming in vaccine efficacy and showed specific profiles detectable as early as two days after immunization. The most efficient candidate, measles vector expressing simultaneously LASV glycoprotein and nucleoprotein, will be soon evaluated in phase I clinical trial. Overall design: 3 vaccines, 5 time points (day 0, 2, 4, 9 and 14 after immunization), 4 replicates per condition