《生命科学》 2021, 33(1): 26-35

马传染性贫血病毒弱毒疫苗致弱及免疫保护机制研究进展

王雪峰 , 张相敏 , 林跃智 , 杜　承 , 王晓钧^*

中国农业科学院哈尔滨兽医研究所，兽医生物技术国家重点实验室，哈尔滨 150069

摘　要：

马传染性贫血病毒(equine infectious anemia virus, EIAV)弱毒疫苗是中国科学家在20世纪70年代研制成功的世界上首例慢病毒疫苗，是迄今为止唯一在临床大规模应用的慢病毒弱毒疫苗。EIAV弱毒疫苗的成功应用不仅消除了该疫病对马业的威胁，而且在学术上突破了慢病毒不能免疫的理论。该疫苗克服了灭活疫苗免疫原性差的难点，能有效地提供对同源和异源毒株的免疫保护。因此，在分子水平上阐明EIAV弱毒疫苗的减毒机理和免疫保护机制对于研究慢病毒免疫保护具有极其重要的科学意义。作者所在的研究团队多年来一直从事EIAV弱毒疫苗的致弱机理及其诱导免疫保护机制的研究，解析了EIAV弱毒疫苗及其强毒株的基因组进化特征、揭示了疫苗致弱规律和疫苗有效组成、提出了“EIAV弱毒疫苗可能起源于EIAV准种的一个小分支”的假说；发现EIAV弱毒疫苗可有效激活天然免疫和特异性免疫，早期诱导的高水平细胞免疫与免疫保护呈正相关；证明了疫苗株的抗原多样性组成是其诱导保护性免疫应答的关键因素。相关研究成果拓展了慢病毒疫苗研究理论和实践认知，可为其他慢病毒尤其是HIV-1免疫原的设计以及免疫保护理论提供有价值的参考。

通讯作者：王晓钧 , Email:wangxiaojun@caas.cn

Research progress on attenuation and immune protection mechanism of an attenuated equine infectious anemia virus vaccine

WANG Xue-Feng , ZHANG Xiang-Min , LIN Yue-Zhi , DU Cheng , WANG Xiao-Jun^*

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China

Abstract:

The attenuated equine infectious anemia virus (EIAV) vaccine developed by Chinese scientists in the 1970s is the first lentiviral vaccine that was approved safe and effective after being applied country-widely and provided a wonderful model for the study of protective immunity to lentiviruses. The successful application of attenuated EIAV vaccine not only eliminates the threat to the horse industry, but also breaks the theory that lentivirus cannot be immunized. The vaccine overcomes the difficulty of poor immunogenicity of inactivated EIAV vaccine and can effectively provide immune protection against homologous and heterologous strains. Therefore, elucidating the mechanism of attenuation and immune protection of the attenuated EIAV vaccine at the  molecular level is of great scientific significance for studying the vaccinology of lentivirus. In an in-deep study on the attenuation and induced immune protection mechanism of attenuated EIAV vaccine in recent years, we revealed the pattern of virus attenuating and the effective composition of vaccine, and proposed that the attenuated EIAV vaccine may originate from a small branch of EIAV quasispecies. It was found that EIAV vaccine could activate innate and adaptive immunity effectively, and the induced high level of cellular immunity in the earlier phases was positively correlated with immune protection in vaccine-inoculated horses. It was proved that the antigen diversity composition of vaccine strains is the key factor to induce protective immune response. Relevant research results have expanded the theories and practical cognition of lentivirus vaccine research, and may provide valuable reference for the design of other lentiviruses, especially HIV-1 immunogens, and immune protection theories.

Communication Author：WANG Xiao-Jun , Email:wangxiaojun@caas.cn