Development and Pathogenicity Analysis of a meq-gene-edited Candidate Marek's Disease Vaccine Strain Generated from a Hypervirulent MDV Variant
Marek's disease(MD),caused by Marek's disease virus(MDV),is one of the most im-portant immunosuppressive and neoplastic diseases.It can be prevented and controlled with MD vaccines,but the virulence of epidemic MDV strains persistently increases under the highly im-mune pressure of widely used MD vaccines.Recent studies have found that the classical MD vac-cines are no longer able to provide ideal immune protection for the current prevalent hypervirulent MDV(HV-MDV)variant,which implies the urgent need to develop a new generation of highly effective MD vaccines.Presently,we have used the newly isolated HV-MDV variant HNSQ01 as the parental virus,first passaged on CEF monolayers in vitro,to generate a meq gene-edited and knocked out mutant of SQ01Δmeq utilizing the CRISPR/Cas9-based gene editing technology.A series of experiments and analysis have demonstrated a stable MD vaccine candidate strain of SQ01Δmeq has been successfully generated.Furthermore,the pathogenicity analysis was per-formed with 1-day-old specific-pathogen-free(SPF)chickens for virus challenge experiments.During the 77-days animal experiments,the parental HNSQ01 had caused serious atrophy of host immune organs and inhibited the growth of virus-challenged birds,together with the 100％MD morbidity,100％mortality and 80％gross tumor occurrence.However,SQ01Δmeq had not caused the immunosuppression or inhibited the growth of virus-challenged birds,together with the 0％rates of MD morbidity,mortality and tumor occurrence.Our data indicate that the gener-ation of SQ01Δmeq provides an important basis for the future research and development of novel efficient genetically engineered MD vaccines.
万方数据
维普
