Single-dose intranasal AdC68-vectored vaccines rapidly protect Syrian hamsters against lethal Nipah virus infection

Nipah virus (NiV) infection is highly lethal in humans, and the development of vaccines that provide rapid protection is critical for addressing NiV outbreaks. In this study, we demonstrate that a single intranasal immunization with the chimpanzee adenoviral-vectored NiV vaccine, AdC68-F, induced robust and sustained cellular and humoral responses in BALB/c mice, and provided complete protection against challenge with the NiV-Malaysia strain (NiV-M) in Syrian hamsters. Notably, AdC68-F, administered at a dose of 5 × 10⁹ viral particles, offered a complete prophylactic protection window as few as 7 days before exposure to a lethal NiV-M challenge. Furthermore, passive transfer of sera from AdC68-F or AdC68-G immunized animals conferred complete protection against NiV-M infection in naive hamsters. These findings underscore the pivotal role of antigen-specific immunity in controlling NiV infection and highlight the potential of single-dose intranasal AdC68-based NiV vaccines for rapid protection during outbreaks. By providing rapid and effective protection, these vaccines could help reduce human-to-human transmission and aid in curbing NiV outbreaks.