A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the emergent vesicular stomatitis virus (VSV) viral vector vaccine for Lassa fever.

There are currently no prophylactic vaccines licensed to protect against Lassa fever caused by Lassa virus (LASV) infection. The Emergent BioSolutions (EBS) vaccine candidate, EBS-LASV, is being developed for the prevention of Lassa fever. EBS-LASV is a live-attenuated recombinant Vesicular Stomatitis Virus (rVSV)-vectored vaccine encoding the surface glycoprotein complex (GPC) from LASV and has two attenuating vector modifications: a gene shuffle of the VSV N gene and a deletion of the VSV G gene. Several preclinical safety studies demonstrate that EBS-LASV is safe when administered to animals. Likewise, in non-human primate immunogenicity and efficacy studies, administration of EBS-LASV produces a cellular and humoral immune response that fully protects NHPs from a lethal Lassa virus challenge. Together, these studies supported a first-in-human dose-escalation, safety, and immunogenicity clinical study. This paper uses a viral vector vaccine safety template developed by the Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group to review the features of the rVSV-vectored EBS-LASV vaccine candidate and provides a high-level summary of safety findings from preclinical studies and the Phase 1 clinical study.