Markoff L
Laboratory of Vector-borne Virus Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852-1448, USA.
Vaccine. 2000 May 26;18 Suppl 2:26-32. doi: 10.1016/s0264-410x(00)00038-4.
Although an effective killed virus vaccine to prevent illness due to Japanese encephalitis virus (JEV) infection exists, many authorities recognize that a safe, effective live JEV vaccine is desirable in order to reduce the cost and the number of doses of vaccine required per immunization. A large-scale clinical efficacy trail for such a vaccine would be both unethical and impractical. Therefore, a surrogate for the efficacy of JE vaccines should be established. Detection of virus-neutralizing antibodies in sera of vaccinees could constitute such a surrogate for efficacy. Field studies of vaccinees in endemic areas and studies done in mice already exist to support this concept. Also, titers of virus-neutralizing antibodies are already accepted as a surrogate for the efficacy of yellow fever virus vaccines and for the efficacy of other viral vaccines as well. In developing a correlation between N antibody titers and protection from JEV infection, standard procedures must be validated and adopted for both measuring N antibodies and for testing in animals. A novel live virus vaccine could be tested in the mouse and/or the monkey model of JEV infection to establish a correlation between virus-neutralizing antibodies elicited by the vaccines and protection from encephalitis. In addition, sera of subjects receiving the novel live JEV vaccine in early clinical trials could be passively transferred to mice or monkeys in order to establish the protective immunogenicity of the vaccine in humans. A monkey model for JEV infection was recently established by scientists at WRAIR in the US. From this group, pools of JEV of known infectivity for Rhesus macaques may be obtained for testing of immunity elicited by live JE vaccine virus.
尽管存在一种有效的灭活病毒疫苗可预防日本脑炎病毒（JEV）感染所致疾病，但许多权威机构认识到，为降低成本和每次免疫所需的疫苗剂量数，一种安全、有效的JEV活疫苗是可取的。针对这种疫苗进行大规模临床疗效试验既不道德也不切实际。因此，应建立JEV疫苗疗效的替代指标。检测疫苗接种者血清中的病毒中和抗体可构成这样一种疗效替代指标。在流行地区对疫苗接种者进行的现场研究以及在小鼠身上进行的研究已存在，以支持这一概念。此外，病毒中和抗体滴度已被公认为黄热病病毒疫苗疗效以及其他病毒疫苗疗效的替代指标。在建立N抗体滴度与预防JEV感染之间的相关性时，必须验证并采用用于测量N抗体和在动物身上进行检测的标准程序。一种新型活病毒疫苗可在JEV感染的小鼠和/或猴模型中进行测试，以建立疫苗诱导的病毒中和抗体与预防脑炎之间的相关性。此外，在早期临床试验中接受新型JEV活疫苗的受试者的血清可被动转移到小鼠或猴子身上，以确定该疫苗在人类中的保护性免疫原性。美国陆军研究所以及研究所的科学家最近建立了一种JEV感染的猴模型。从该群体中，可获得对恒河猴具有已知感染性的JEV毒株库，用于测试活JE疫苗病毒诱导的免疫力。
