本帖最后由 chenzongxiang 于 2016-12-2 09:25 编辑
来源：科技日报 / 2016-12-02
美国东部时间12月1日，全球最大的科技新闻工作站SciPak向全球媒体发布，国际顶级期刊《科学》2日发表中国科学家题为《制备复制缺陷的活流感病毒疫苗》的研究进展，称发明了人工控制病毒复制，从而将病毒直接转化为疫苗的技术，这一发现颠覆了病毒疫苗研发的理念，成就了活病毒疫苗的重大突破。 该研究由北京大学药学院天然药物及仿生药物国家重点实验室主任周德敏教授/张礼和院士课题组完成。 在国家创新药物专项、基金委和国家原973计划的支持下，课题组以流感病毒为模型，在保留病毒完整结构和感染力的情况下，仅突变病毒基因组的一个三联码，使流感病毒由致命性传染源变为预防性疫苗，再突变三个以上三联码，病毒由预防性疫苗变为治疗病毒感染的药物。并且随着三联码数目的增加而药效增强。这一“四两拨千斤”技术不仅使疫苗研发不再复杂，而且摆脱了对病毒生物学知识获得的依赖，并适用于几乎所有病毒。 周德敏说，他们研发的疫苗是活病毒疫苗，即保留了野生流感病毒完全的感染力，只是将它感染人体后在细胞内的复制和生产新病毒能力剔除了。通过这种方式保留了病毒感染人体引发的全部免疫原性，即体液免疫、鼻腔黏膜免疫和T-细胞免疫，而对人体的毒性被控制了。此方法完全不同于当前使用的仅部分免疫的灭活疫苗，也不同于仍然保留弱复制能力而有毒性危险的减活疫苗。该通用方法可以做包括艾滋病、SARS和埃博拉出血热等几乎任意致命性病毒的疫苗和治疗性生物技术药物，并可用来开发影响国防安全的预防性生化武器。 Protecting by changing the codeLive attenuated vaccines can be very potent, but their potential to revert to their pathogenic form limits their use. In an attempt to get around this, Si et al. expanded the genetic code of influenza A viruses. They propagated viruses that were mutated to encode premature termination codons (PTCs) in a cell line engineered to be able to express these flu proteins. Despite not being able to replicate in conventional cells, PTC-containing viruses were highly immunogenic and protected mice, guinea pigs, and ferrets against influenza challenge. AbstractThe conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)–harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell–mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
Generation of influenza A viruses as live but replication-incompetent virus vaccines | Science http://science.sciencemag.org/content/354/6316/1170
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