Host-range restriction of chimeric yellow fever-West Nile vaccine in fish crows (Corvus ossifragus)

We evaluated a recombinant virus chimera, ChimeriVax-WN, in which the West Nile virus (WNV) surface protein genes (pre-membrane [prM] and envelope [E]) are substituted into the genome of the 17D vaccine strain yellow fever virus (YF-17D), as a vaccine candidate for protection of birds from WNV disease. Using fish crows (Corvus ossifragus) as a model, we found that none of eight crows that received two high doses of vaccine (approximately 100,000 plaque-forming units [PFU]) developed viremia and only one developed WNV-neutralizing antibodies. When challenged with subcutaneous injection of 2,000 PFU of WNV (NY99 strain), all eight developed viremia levels similar to unvaccinated control birds (n = 4). Two of the vaccinated birds died of the infection, compared with no mortality in the four controls. To further investigate the failure of the vaccine, we inoculated chickens with both the vaccine and YF-17D and found no evidence of replication with either of these viruses. These data indicate that this vaccine candidate failed to protect birds from the morbidity and mortality attributed to WNV infections. However, if used in mammals, this recombinant viral vaccine is unlikely to inadvertently enter a natural transmission cycle with birds as amplifying hosts.