宿主microRNA靶向介导的减毒活疫苗研究进展

Advances in live attenuated vaccines by targeting host microRNAs

疫苗是预防病毒性传染病的最有效手段,包括减毒活疫苗、灭活疫苗、核酸疫苗和基因工程疫苗等。减毒活疫苗模拟了病毒的感染过程,能有效诱导机体产生体液和细胞免疫应答,在临床上得到广泛应用。传统的减毒活疫苗一般通过连续传代获得,研发成本高。微小RNA(microRNA,miRNA)靶向调节是新近发现的宿主调控基因表达的重要手段,具有明确的组织特异性和种属特异性。通过反向遗传学技术能够将特异的宿主miRNA靶向序列有效整合入病毒基因组,从而实现对病毒生物学特征的有效调节,在减毒活疫苗设计与研发领域有着良好的应用前景。该文综述了miRNA靶向介导的减毒策略及其在疫苗设计中的研究进展。

Vaccine immunization represents the most effective strategy against viral infections.Antiviral vaccine candidates currently include live attenuated vaccine,inactivated vaccine,DNA vaccine and genetic engineering vaccine.Live attenuated vaccines,eliciting efficient humoral and cellular immune response by simulating natural virus infection,are clinically widely used.Traditionally,live attenuated vaccine strains are obtained by serial passaging in vitro or in vivo,a costly procedure accumulating random mutations.microRNA（miRNA）-targeting host gene regulation exhibits high species and tissue specificity.Introducing certain miRNA target sequence into viral genome by reverse genetic technique can effectively attenuate virus strains,which has great potential in vaccine design and development.In this article,attenuation strategies and progress in its application in vaccine research are disscussed.