Defining Challenge Conditions for Nipah Virus in the Syrian Golden Hamster Model: Effects of Dose, Exposure Route and Viral Strain

Nipah virus (NiV) is a highly pathogenic zoonotic virus for which no licensed vaccines or therapeutics are currently available, necessitating well-characterised animal models to support countermeasure development. This study aimed to establish an appropriate challenge dose in the Syrian golden hamster model at the UK Health Security Agency (UKHSA), incorporating both intraperitoneal (i.p.) and intranasal (i.n.) routes of infection and two clinically relevant strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B). Due to a different challenge doses and susceptibilities of hamsters to NiV being reported in the literature, there is a prerequisite to define the model parameters upon establishment in a new facility. Dose-ranging studies were performed across multiple independent experiments assessing survival, clinical progression and histopathological outcomes. Challenge via the i.p. route produced consistent and severe disease using an infectious dose of 103 TCID50 for both strains. In contrast, animals were more susceptible to infection via i.n. challenge with a dose of 10 TCID50 resulting in uniform lethality. For both challenge routes, respiratory and neurological disease manifestations were observed. These distinct disease phenotypes were supported by histopathological findings and viral RNA distribution in affected organs. Differences between strains were evident, with NiV-B showing a tendency towards a broader pulmonary pathology at lower doses after i.n. challenge. Collectively, these findings demonstrate that challenge dose, route of exposure, and viral strain influence disease outcomes in the hamster model.