Monath Thomas P, Liu Jian, Kanesa-Thasan Niranjan, Myers Gwendolyn A, Nichols Richard, Deary Alison, McCarthy Karen, Johnson Casey, Ermak Thomas, Shin Sunheang, Arroyo Juan, Guirakhoo Farshad, Kennedy Jeffrey S, Ennis Francis A, Green Sharone, Bedford Philip
Acambis, 38 Sidney Street, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6694-9. doi: 10.1073/pnas.0601932103. Epub 2006 Apr 14.
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-WN02 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from an infectious clone of yellow fever (YF) 17D virus in which the premembrane and envelope genes of 17D have been replaced by the corresponding genes of WN virus.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 log10 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 WN disease.
西尼罗河（WN）病毒是引起发热性皮疹和脑炎的重要病因。自1999年侵入美国以来，已报告了超过19000例人类病例。持续流行的威胁促使人们努力研发疫苗。嵌合疫苗ChimeriVax-WN02是一种减毒活重组疫苗，由黄热病（YF）17D病毒的感染性克隆构建而成，其中17D病毒的前膜和包膜基因已被WN病毒的相应基因所取代。在猴子身上进行的临床前试验确定了疫苗病毒在体内的复制部位。ChimeriVax-WN02和YF 17D具有相似的生物分布，但增殖动力学不同。主要的复制部位是皮肤和淋巴组织，通常不涉及重要器官。病毒在第7天从血液中清除，在第14天左右从组织中清除。在一项临床研究中，健康成年人接种了5.0 log(10) 蚀斑形成单位（PFU）（n = 30）或3.0 log10 PFU（n = 15）的ChimeriVax-WN02、市售YF疫苗（YF-VAX，n = 5）或安慰剂（n = 30）。接受疫苗接种的受试者中不良事件的发生率与安慰剂组相似。在45名接种ChimeriVax-WN02的受试者中有42名（93%）检测到短暂病毒血症，在5名接种YF-VAX的受试者中有4名（80%）检测到短暂病毒血症。所有受试者分别产生了针对WN或YF的中和抗体，大多数受试者产生了特异性T细胞反应。ChimeriVax-WN02单剂量接种后能迅速引发强烈的免疫反应，是预防WN疾病值得进一步评估的有前景的候选疫苗。
