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受控人体感染模型是否是研发HCV疫苗的快速路径
Controlled Human Infection Model — Fast Track to HCV Vaccine?


T. Jake Liang ... 传染病 • 2021.09.23
相关阅读
• 丙型肝炎病毒感染供者的心肺被安全移植到HCV阴性受者体内 • glecaprevir和pibrentasvir复方药用于治疗丙型肝炎病毒感染合并重度肾功能损害患者 • 慢性肝炎的全球消除

1989年,Houghton及其同事发现了丙型肝炎病毒(HCV)这一神出鬼没的非甲、非乙型肝炎病毒,这标志着寻找该病毒的漫长征程结束。在接下来20年间,我们见证了丙型肝炎治疗领域的空前变革,这一变革建立在上述突破的基础上,运用了现代科学,并且产生了可治愈95%以上HCV感染者的治疗方案。这一壮举代表了医学科学领域的最高成就,最终使Michael Houghton、Harvey J. Alter和Charles M. Rice获得2020年诺贝尔生理学或医学奖。当我们沉浸在这一胜利带来的荣誉中时,一定要提醒自己,我们与这一病毒的战斗远未结束:全球每年仍有数十万人死于这一疾病,而且由于阿片类药物滥用,新发感染继续在包括北美在内的世界许多地区肆虐1。如果说我们从历史中吸取了什么经验教训的话,那就是消除一种传染病既需要有效的疫苗,也需要成功的全球接种策略。消除HCV也需要疫苗,这一点毫无例外。

正如之前论文所指出的那样,通往HCV疫苗的道路充满了困难2,3。10多年前生效的黑猩猩实验暂停令实际上停用了HCV疫苗研发中唯一可行的动物模型,尽管暂停令并未明确禁止将黑猩猩用于该目的。由于缺乏可供临床前试验使用的替代动物模型4,以及由于人们认为高效疗法将足以在全球范围内控制病毒,因此新疫苗研发工作陷入了停滞。最近,在一项大规模人体试验中,一种腺病毒载体HCV疫苗的结果令人失望5,这说明应用当前方法研发和检测有效疫苗面临挑战。目前只有另外一种候选疫苗(基于重组HCV包膜蛋白)正在临床研发中,该疫苗在黑猩猩实验暂停令实施之前在黑猩猩身上进行了试验3。在重新允许使用黑猩猩之前,参与HCV疫苗研发工作的研究者基本再无其他选择。尽管在人体内开展大规模、受控的疫苗效力试验仍有必要,但本文提出了一个旨在重新启动HCV疫苗研发工作的可能的中间步骤,即基于受控人体感染模型(CHIM)的研究。

CHIM已有数百年的应用历史,它指的是为了增进医学知识,尤其是为了研发疫苗,在受控条件下故意使用传染源感染人体。从1796年爱德华·詹纳医师试验天花疫苗开始,该模型已应用于超过25种传染病,其中包括黄热病、霍乱、疟疾、登革热,以及最近的COVID-19 6。CHIM为疫苗研发提供了至关重要的中间阶段,其主要作用是降低风险和成本,以及帮助我们为之后的更大规模2期和3期试验选择更有前景的候选疫苗。





作者信息

T. Jake Liang, M.D., Jordan J. Feld, M.D., Andrea L. Cox, M.D., Ph.D., and Charles M. Rice, Ph.D.
From the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda (T.J.L.), and the Division of Infectious Diseases, Johns Hopkins University, Baltimore (A.C.) — both in Maryland; the Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto (J.J.F.); and the Laboratory of Virology and Infectious Disease, Rockefeller University, New York (C.M.R.). Address reprint requests to Dr. Liang at the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 10-9B16, 10 Center Dr., Bethesda, MD 20892-1800, or at jliang@nih.gov.

 

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