Preexisting immunity does not prevent efficacy of VSV-based filovirus vaccines in nonhuman primates.

Ebola virus (EBOV) and Marburg virus (MARV) made headlines in the past decade causing outbreaks of human disease in previously nonendemic yet overlapping areas. While EBOV outbreaks can be mitigated with licensed vaccines and treatments, there is not yet a licensed countermeasure for MARV. Here, we used nonhuman primates (NHPs) previously vaccinated with VSV-MARV and protected against lethal MARV challenge. After a resting period of 9 months, these NHPs were re-vaccinated with VSV-EBOV and challenged with EBOV resulting in 75% survival. Surviving NHPs developed EBOV GP-specific antibody titers and no viremia or clinical signs of disease. The single vaccinated NHP succumbing to challenge showed the lowest EBOV GP-specific antibody response after challenge supporting previous findings with VSV-EBOV that antigen-specific antibodies are critical in mediating protection. This study again demonstrates that VSVΔG-based filovirus vaccine can be successfully used in individuals with pre-existing VSV vector immunity highlighting the platform's applicability for consecutive outbreak response.