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A live, attenuated recombinant West Nile virus vaccine

机译:减毒活重组西尼罗河病毒疫苗

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West Nile (WN) virus is an important cause of febrile exanthem and encephalitis. Since it invaded the U.S. in 1999, > 19,000 human cases have been reported. The threat of continued epidemics has spurred efforts to develop vaccines. ChimeriVax-WNO2 is a live, attenuated recombinant vaccine constructed from an infectious clone of yellow fever (YF) 17D virus in which the premembrane and envelope genes of 17D have been replaced by the corresponding genes of WIN virus. Preclinical tests in monkeys defined sites of vaccine virus replication in vivo. ChimeriVax-WN02 and YF 17D had similar biodistribution but different multiplication kinetics. Prominent sites of replication were skin and lymphoid tissues, generally sparing vital organs. Viruses were cleared from blood by day 7 and from tissues around day 14. In a clinical study, healthy adults were inoculated with 5.0 log(10) plaque-forming units (PFU) (n = 30) or 3.0 log(10) PFU (n = 15) of ChimeriVax-WN02, commercial YF vaccine (YF-VAX, n = 5), or placebo (n = 30). The incidence of adverse events in subjects receiving the vaccine was similar to that in the placebo group. Transient viremia was detected in 42 of 45 (93%) of ChimeriVax-WN02 subjects, and four of five (80%) of YF-VAX subjects. All subjects developed neutralizing antibodies to WN or YF, respectively, and the majority developed specific T cell responses. ChimeriVax-WN02 rapidly elicits strong immune responses after a single dose, and is a promising candidate warranting further evaluation for prevention of WIN disease.
机译:西尼罗河病毒(WN)是高热性发烧和脑炎的重要原因。自1999年入侵美国以来,据报有19,000多例人类病例。持续流行的威胁促使人们开发疫苗。 ChimeriVax-WNO2是一种减毒活疫苗,由黄热病(YF)17D病毒感染性克隆构建而成,其中17D的前膜和包膜基因已被WIN病毒的相应基因取代。猴子的临床前测试定义了体内疫苗病毒复制的部位。 ChimeriVax-WN02和YF 17D具有相似的生物分布,但增殖动力学不同。复制的主要部位是皮肤和淋巴组织,通常不留重要器官。在第7天时从血液中清除病毒,在第14天时从组织中清除病毒。在一项临床研究中,健康成人接种了5.0 log(10)噬菌斑形成单位(PFU)(n = 30)或3.0 log(10)PFU( ChimeriVax-WNO2,商用YF疫苗(YF-VAX,n = 5)或安慰剂(n = 30)的n = 15)。接受疫苗的受试者中不良事件的发生率与安慰剂组相似。在ChimeriVax-WN02受试者中的45名中有42名(93%),在YF-VAX受试者中有五名中的四名(80%)检测到短暂病毒血症。所有受试者均分别产生针对WN或YF的中和抗体,而大多数受试者均产生特异性T细胞应答。 ChimeriVax-WN02在单剂后迅速引起强烈的免疫反应,是有希望的候选物,值得进一步评估其对WIN疾病的预防。

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