West Nile virus (WNV) causes significant disease, yet no vaccines exist to prevent WN disease in humans. We have previously reported that RepliVAX WN is a safe and efficacious vaccine in mouse and hamster models of WN disease. Here, we report that vaccination of hamsters with RepliVAX WN induces antibody responses that remain stable for at least 6 months. Furthermore, animals challenged with virulent WNV 6 months after vaccination were protected from disease as well as those challenged 2 months post-vaccination, with no vaccinated animals succumbing to WNV challenge. These results indicate that RepliVAX is capable of inducing durable protective immunity after a single dose.