Lassa fever outbreaks hit West African countries every year and there is still no licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine that induces protective immunity in cynomolgus monkeys one month or more than a year before Lassa virus infection and that is able to protect against divergent viral strains. Given the limited dissemination area of Lassa virus during outbreaks and the high risk of nosocomial transmission, a vaccine that induces rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. We tested whether the time to protection could be reduced after immunization by challenging MeV pre-immune cynomolgus monkeys 16 or 8 days after a single shot of MeV-NP. None of the immunized monkeys developed disease and they rapidly controlled viral replication. Animals immunized eight days before the challenge were the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated an hour after the challenge. These animals did not develop any protective immune responses and presented the same lethal disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine. Here, we include the experimental design to perfom the statistical analyses and the departing count matrix (raw_counts.txt) cell types: PBMC , 51 samples Conditions: 3 groups, 9 specimens (cynomolgus monkeys) 6 time points day 0, d 3, day 6, day 9, day 12 and day 15 after LASV infection Diff analysis was performed using DESeq2 package with the following design. m1 = model.matrix(~ Subject + Group*Subject + Group*Timepoint , data = target)

This study was funded by a grant from the Coalition for Epidemic Preparedness and Innovations (CEPI-CfP-001) to S. Baize and by a grant from the Agence Nationale de la Recherche (ANR-21-CE18-0004-01) to M. Mateo.