体外转录的自我复制型mRNA疫苗研究进展*

自我复制型mRNA是一种灵活的疫苗平台,该平台的开发基于甲病毒表达载体,其中复制必需基因得以完整保留,而结构蛋白基因则被来自病原的抗原基因替换。由于避免了病原培养、毒力返强和现存免疫的干扰,使其成为疫苗快速设计的理想平台。大量研究数据显示,此类疫苗可应用在人、小鼠、兔、猪、禽甚至鱼类体内诱导体液免疫和细胞免疫。过去,自我复制mRNA疫苗的研究采用重组单载体的模式,基因组骨架来源于辛德毕斯病毒、塞姆利基森林病毒和委内瑞拉马脑炎病毒。现在,反式复制型RNA和核酸修饰的反式复制型RNA作为下一代技术平台被寄予厚望。对基于甲病毒表达载体的mRNA疫苗技术的研究进展进行概述,重点介绍针对以流感病毒、新型冠状病毒和寨卡病毒等为代表的自我复制型mRNA疫苗研究现状,并探讨了该技术平台的未来发展方向。

In Vitro Transcribed Self-amplifying mRNA Vaccines

Self-amplifying mRNA vaccine is a versatile vaccine platform developed from alphavirus expression vector in which the viral replication genes are intact but those viral structural genes are replaced with antigen genes derived from pathogens. These vaccines have emerged as ideal modalities for rapid vaccine design, avoiding the problem of pathogen culture, reversion to pathogenicity and pre-existing immunity. Numerous studies demonstrated that these vaccines could be employed to induce humoral and cellular immune responses in human, mice, rabbits, pigs, avian and even fish. During the past years, focus has been on the use of recombinant single vectored self-replicating mRNA derived from the genome backbone of Sindbis virus, Semliki forest virus, and Venezuelan equine encephalitis virus. Now trans-amplifying RNA and nucleotide modified trans-amplifying RNA vaccines have come into focus as promising next-generation technology platforms for vaccine development. An overview of recent advance in self-replicating RNA vaccines developed from alphavirus expression vectors was presented, with an emphasis on current state of SAM vaccine approaches against emerging infectious diseases, such as influenza A virus, SARS-CoV-2, and ZIKA virus, and provide perspectives on the future of this technology platform.