Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters

•A single dose of VSV-ΔG-based vaccines expressing Nipah glycoproteins protected hamsters.•VSV-ΔG-based NiV vaccines induced high levels of serum neutralizing antibodies with one dose.•Lack of detectable anamnestic immune responses indicates potential sterilizing immunity.

Nipah virus (NiV) continues to cause outbreaks of fatal human encephalitis due to spillover from its bat reservoir. We determined that a single dose of replication-defective vesicular stomatitis virus (VSV)-based vaccine vectors expressing either the NiV fusion (F) or attachment (G) glycoproteins protected hamsters from over 1000 times LD50 NiV challenge. This highly effective single-dose protection coupled with an enhanced safety profile makes these candidates ideal for potential use in livestock and humans.