A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters

Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development. Author summary Nipah virus was discovered in 1998 after an outbreak in Malaysia. Since then, several outbreaks have been reported in Bangladesh and India. Although most outbreaks are relatively small, a very high case-fatality rate is reported (75%). Furthermore, human-to-human transmission has been reported. Currently, no approved vaccine or countermeasure exist. In this manuscript, we discuss a vaccine based on a chimpanzee adenovirus. Importantly, the vaccine vector (ChAdOx1) is in clinical trials. In the work presented here, we show that this vaccine is fully protective against both genotypes of Nipah virus. Furthermore, we observe partial protection against Hendra virus, a related virus. Antibodies produced upon vaccination with our vaccine alone are partially protective against Nipah virus. This is an important step forwards towards the development of an approved vaccine for Nipah virus.