A recombinant VSV-vectored vaccine rapidly protects nonhuman primates against heterologous lethal Lassa fever

Lassa virus (LASV) is recognized by the World Health Organization as one of the top five pathogens likely to cause a severe outbreak. A recent unprecedented resurgence of LASV in Nigeria caused by genetically diverse strains underscores the need for licensed medical countermeasures. Single-injection vaccines that can rapidly control outbreaks and confer long-term immunity are needed. Vaccination of cynomolgus monkeys with a recombinant vesicular stomatitis virus vector expressing the glycoprotein precursor of LASV lineage IV strain Josiah (rVSVΔG-LASV-GPC) induces fast-acting protection in monkeys challenged 3 or 7 days later with a genetically heterologous lineage II isolate of LASV from Nigeria, while nonspecifically vaccinated control animals succumb to challenge. The rVSVΔG-LASV-GPC vaccine induces rapid activation of adaptive immunity and the transcription of natural killer (NK) cell-affiliated mRNAs. This study demonstrates that rVSVΔG-LASV-GPC may provide rapid protection in humans against LASV infections in cases where immediate public-health intervention is required.