马立克病基因工程疫苗研究进展

Advances in novel genetically engineered vaccines against Marek's disease

马立克病(MD)是由马立克病病毒(MDV)感染引起的严重危害世界养禽业健康发展的一种重要的家禽免疫抑制病与肿瘤病,是人类历史上第一个可以通过疫苗免疫接种成功预防肿瘤疾病发生的案例。对雏鸡早期接种MD疫苗,可有效控制MD肿瘤的发生。随着MD疫苗的广泛使用和长期免疫压力,MDV流行毒株也在不断进化、毒力增强或变异,部分毒株已突破现有商品疫苗的免疫保护,导致MD疫情在全球频繁暴发。自MD疫苗问世至今,已有多种MD疫苗研制成功,并且二价疫苗、三价疫苗、重组载体疫苗、基因缺失或插入的MD疫苗等也在不断被研究和优化。利用各种新兴的生物学技术,如细菌人工染色体(BAC)、基因同源重组和CRISPR/Cas9基因编辑等来开展MD基因工程疫苗研究,已成为病毒病疫苗研究领域的最新热点。本文回顾了过去50年来MD疫苗研究历程及巨大成就,并全面综述了当前国内外MD基因工程疫苗和基因编辑疫苗所取得的最新研究进展,同时也对现有MD商品疫苗免疫预防所面临的新问题、新挑战和未来前景进行了展望,以期为下一代新型高效的MD疫苗创制提供重要参考。

Marek's disease(MD)is an immune inhibition disease and oncosis caused by MD virus,which has brought loss to the poultry industry in the world.MD vaccine has been the first case in history where the tumor disease has been successfully prevented by anti-viral vaccine immunization.However,under circumstance of the worldwide use of MD vaccines and long-term high immune pressure,epidemic strains of Marek's disease virus(MDV)have persistently evolved,becoming more virulent or mutating,and some of the strains have broken through the immune protection of the existing classical commercial vaccines,resulting in frequent outbreaks of MD cases around the world.Since the first report on MD vaccine,a variety of vaccines have been successfully developed and optimized.The use of various emerging bio-logical technologies,such as bacterial artificial chromosomes(BAC),genomic homologous recombination and CRISPR/Cas9-based gene ed-iting,to develop genetically engineered MD vaccines has become the latest hot spot in the studies of novel MD vaccines.Herein,we have o-verviewed the historical development of classical MD vaccines and related great achievements in the past 50 years,and comprehensively re-viewed the latest progress in research on genetically engineered MD vaccines and gene-edited vaccines.We have also discussed the emerging problems,new challenges and future prospects of the existing commercial MD vaccines for the control of the disease,in the hope of offering important reference for development of next-generation,new and more efficient MD vaccines.