Characterization of West Nile virus live vaccine candidates attenuated by capsid deletion mutations

Protein C deletion mutants of West Nile virus (WNV) were evaluated for their potential use as live virus vaccine candidates in vivo. Double and triple mutants carrying small deletions and second-site point mutations, as well as mutants with large deletions of 36 and 37 amino acid residues were tested in a stringent mouse challenge model. The mutant viruses were found to be non-pathogenic and to induce protective immunity in a wide range of inoculation doses (10¹–10⁶ FFU). Furthermore, the effects of combining three different previously identified resuscitating point mutations, as well as the combination of a large protein C deletion with a deletion mutation in the 3′ non-coding region were studied. The data indicate that the production of safe and efficacious WNV live vaccines based on protein C deletion mutations is feasible.