Monath T P, Arroyo J, Miller C, Guirakhoo F
Acambis Inc., 38 Sidney Street, Cambridge, Massachusetts 02139, USA.
Curr Drug Targets Infect Disord. 2001 May;1(1):37-50. doi: 10.2174/1568005013343254.
Within the past 5 years, West Nile encephalitis has emerged as an important disease of humans and horses in Europe. In 1999, the disease appeared for the first time in the northeastern United States. West Nile virus (a mosquito-borne flavivirus) has flourished in the North American ecosystem and is expected to expand its geographic range. In this review, the rationale for a human and veterinary vaccine is presented and a novel approach for rapid development of a molecularly-defined, live, attenuated vaccine is described. The technology (ChimeriVax) is applicable to the development of vaccines against all flaviviruses, and products against Japanese encephalitis (a close relative of West Nile) and dengue are in or are nearing clinical trials, respectively. ChimeriVax vaccines utilize the safe and effective vaccine against the prototype flavivirus -yellow fever 17D- as a live vector. Infectious clone technology is used to replace the genes encoding the pre-membrane (prM) and envelope (E) protein of yellow fever 17D vaccine with the corresponding genes of the target virus (e.g., West Nile). The resulting chimeric virus contains the antigens responsible for protection against West Nile but retains the replication efficiency of yellow fever 17D. The ChimeriVax technology is well-suited to the rapid development of a West Nile vaccine, and clinical trials could begin as early as mid-2002. Other approaches to vaccine development are briefly reviewed. The aim of this brief review is to describe the features of West Nile encephalitis, a newly introduced infectious disease affecting humans, horses and wildlife in the United States; the rationale for rapid development of vaccines; and approaches to the development of vaccines against the disease.
在过去5年里，西尼罗河脑炎已成为欧洲一种重要的人畜共患病。1999年，该病首次出现在美国东北部。西尼罗河病毒（一种由蚊子传播的黄病毒）在北美生态系统中迅速传播，并有望扩大其地理分布范围。在这篇综述中，阐述了研发人用和兽用疫苗的基本原理，并描述了一种快速开发分子定义的、减毒活疫苗的新方法。该技术（嵌合疫苗）适用于开发针对所有黄病毒的疫苗，针对日本脑炎（西尼罗河病毒的近亲）和登革热的产品分别处于临床试验阶段或即将进入临床试验阶段。嵌合疫苗利用针对原型黄病毒——黄热病17D疫苗的安全有效疫苗作为活载体。利用感染性克隆技术，用目标病毒（如西尼罗河病毒）的相应基因替换黄热病17D疫苗编码前膜（prM）和包膜（E）蛋白的基因。由此产生的嵌合病毒含有负责预防西尼罗河病毒的抗原，但保留了黄热病病毒17D的复制效率。嵌合疫苗技术非常适合快速开发西尼罗河疫苗，临床试验最早可能在2002年年中开始。本文还简要回顾了疫苗开发的其他方法。这篇简短综述的目的是描述西尼罗河脑炎的特征，这是一种新出现的影响美国人类、马匹和野生动物的传染病；快速开发疫苗的基本原理；以及针对该疾病的疫苗开发方法。
