SEROLOGY AND VIRULENCE DIVERSITY AMONG OLD-WORLD ARENAVIRUSES, AND THE RELEVANCE TO VACCINE DEVELOPMENT
SEROLOGY AND VIRULENCE DIVERSITY AMONG OLD-WORLD ARENAVIRUSES, AND THE RELEVANCE TO VACCINE DEVELOPMENT
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DOI：
10.1007/bf02122441
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发表时间：
1986-01-01
影响因子：
5.4
通讯作者：
PETERS, CJ
中科院分区：
文献类型：
--
作者：
JAHRLING, PB;PETERS, CJ
拉沙热是西非的一个主要公共卫生问题。迫切需要制定有效的治疗和免疫战略。系统的发展需要更精确地了解拉沙病毒（LV）感染的免疫生物学，必须解决观察到的LV人群的毒力和抗原性标志物的变异性。拉沙热通常被认为是一种单一的疾病实体。然而，最近从利比里亚、塞拉利昂和尼日利亚的住院患者中获得的LV分离株在空斑减少中和试验中显示出对实验室动物（包括豚鼠和食蟹猴）的毒力谱[2]和抗原多样性。中和抗体活性表示为对数中和指数（LNI），其定义为（在对照血清存在下的IOglo噬斑形成单位）-（在免疫血清存在下的IoglO噬斑形成单位）[1]。在这些和其他已知的旧世界沙粒病毒之间建立了交叉中和关系，即淋巴细胞性脉络丛脑膜炎病毒（LCMV）和自然减毒的Lassaqike Mopeia和Mobala病毒，最近分别从莫桑比克和中非共和国的持续感染啮齿动物中分离出来。还建立了这些病毒之间的交叉保护关系，作为经验性开发LV减毒活疫苗的基础，如天然减毒Mopeia病毒所建议的那样[4]。研究了所观察到的交叉保护关系的可能机制。在菌株13豚鼠中检测的78株血清学上无法区分的利比里亚LV分离株的致死模式通常与人类疾病的严重程度相关，但也有明显的例外情况;来自严重fll或致死性感染患者（尤其是孕妇和婴儿）的偶尔分离株对豚鼠完全是良性的。这一观察结果令人担忧，因为豚鼠通常用于监测减毒沙粒病毒活候选疫苗的减毒。来自利比里亚的致死性和良性LV分离株不能通过任何可用的LV单克隆抗体或中和试验相互区分。然而，中和试验确实区分了不同地理来源的LV毒株。西非菌株之间的中和差异不大，但可重复。因此，免疫血浆和LV株来源的地理匹配在选择中可能是重要的。
Lassa Fever is a major public health problem in West Africa. Development of effective treatment and immunization strategies are urgently needed. Systematic development requires a more precise understanding of the immunobiology of Lassa virus (LV) infections, and must address the observed variability of LV populations with respect to markers of virulence and antigenic identity. Lassa Fever is generally considered to be a single disease entity. However, LV isolates recently obtained from hospitalized patients in Liberia, Sierra Leone, and Nigeria exhibited a spectrum of virulence for laboratory animals including guinea pigs and cynomolgus monkeys [2], and antigenic diversity, in plaque reduction neutralization tests. Neutralizing antibody activity was expressed as log neutralization index (LNI) defined as (lOglo plaque-forming units in presence of control serum)-(logl0 plaque-forming units in presence of immune serum)[1]. Cross-neutralization relationships were established among these and the other known Old-World arenaviruses, ie lymphocytic choriomeningitis virus (LCMV) and the naturally attenuated, Lassaqike Mopeia and Mobala viruses, recently isolated from persistently infected rodents in Mozambique and the Central African Republic, respectively. Cross-protective relationships among these viruses were also established as a basis for empirical development of a live attenuated LV vaccine, as had been suggested for the naturally attenuated Mopeia virus [4]. Possible mechanisms for the cross-protective relationships observed were investigated. Lethality patterns for 78 serologically indistinguishable Liberian LV isolates tested in strain 13 guinea pigs generally correlated with the severity of human disease, but there were notable exceptions; occasional isolates from severely fll or fatally infected patients, especially pregnant women and infants, were totally benign for guinea pigs. This observation is alarming since guinea pigs are routinely used to monitor the attenuation of live attenuated arenavirus candidate vaccines. Lethal and benign LV isolates from Liberia could not be discriminated from each other by any of the available LV monoclonal antibodies, nor by neutralization tests. However, the neutralization test did discriminate among LV strains of different geographic origins. Neutralization differences among West African strains were modest, but reproducible. Thus geographic matching of immune plasma and LV strain origins may be important in the selection