A novel neuro-attenuated vaccine candidate with excellent safety and protective efficacy against highly virulent Feline Herpesvirus-1

Feline herpesvirus 1 (FHV-1) is a major pathogen responsible for respiratory, ocular and nervous system symptoms in felines. FHV-1 can remain latenct in ganglia and is difficult to eliminate completely with drug treatment. Currently, commercially FHV-1 vaccines are not sufficiently effective and provide only limited durations of protection. To enhance vaccine efficacy and reduce latent virus in tissues, two gene deletion mutants of FHV-1 conveyed excellent proliferation ability, genetic stability and attenuated FHV-1 virulence were constructed by CRISPR/Cas9-mediated homologous recombination, designated as FHV-△US3 and FHV-△UL50. Recombinant FHV-1 induce stronger cellular and humoral immune responses, as well as better protective effects than those of commercial vaccines. Notably, FHV-△US3 and FHV-△UL50 reveal neuro-attenuated, as viral residue in the trigeminal ganglia are significantly reduced. The knockout of the UL50 gene in FHV-1 has not been previously reported. In this study, we aimed to evaluate the safety and immunogenicity of FHV-△UL50, highlighting its potential as a novel neuroattenuated vaccine candidate.