PASSIVE ANTIBODY THERAPY OF LASSA FEVER IN CYNOMOLGUS MONKEYS - IMPORTANCE OF NEUTRALIZING ANTIBODY AND LASSA VIRUS-STRAIN
PASSIVE ANTIBODY THERAPY OF LASSA FEVER IN CYNOMOLGUS MONKEYS - IMPORTANCE OF NEUTRALIZING ANTIBODY AND LASSA VIRUS-STRAIN
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DOI：
10.1128/iai.44.2.528-533.1984
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发表时间：
1984-01-01
影响因子：
3.1
通讯作者：
PETERS, CJ
中科院分区：
文献类型：
--
作者：
JAHRLING, PB;PETERS, CJ
用灵长类动物或人源免疫血浆被动免疫感染拉沙病毒的食蟹猴，以了解血浆选择和对人拉沙热患者给药的标准。保护效力与中和抗体浓度相关，以log 10中和指数（LNI）表示。通过在s.c.当天i. v.接种血浆稀释液，滴定恢复期Lassa免疫猴血浆的保护效力。接种拉沙病毒（第0天），并在第3天和第6天再次接种。接受未稀释血浆（LNI = 4.1）（每次治疗1 ml/kg）的猴在致死病毒剂量下存活;接受相同血浆1：3稀释（LNI = 2.6）（每次治疗1 ml/kg）的猴死亡。当1：3血浆稀释液的体积增加至每次处理3 ml/kg时，保护作用恢复。稀释血浆≥1：9（LNI = ≤1.5)延迟发作并抑制病毒血症的程度，但在每次治疗3 ml/kg时未能提供保护。免疫增强，定义为增加病毒血症或加速死亡，并没有发生以下不充分的治疗。人恢复期血浆也保护受体猴;血浆的LNI准确预测了死亡率和病毒血症的降低。利比里亚来源的血浆中和利比里亚拉沙菌株比塞拉利昂菌株在体外（LNI = 2.8和1.6，分别）和保护猴有效地对利比里亚菌株。因此，地理来源是选择用于治疗人类拉沙热的最佳血浆的一个因素，因为地理匹配的血浆更可能含有针对同源拉沙病毒株的足够LNI滴度。早期输注高LNI血浆似乎是治疗成功的关键。
Lassa virus-infected cynomolgus monkeys were passively immunized with immune plasma of primate or human origin to gain insight into criteria for plasma selection and administration to human Lassa fever patients. Protective efficacy was correlated with neutralizing antibody concentrations, expressed as a log10 neutralization index (LNI). Convalescent Lassa-immune monkey plasma was titrated for protective efficacy in monkeys by i.v. inoculation with dilutions of plasma on the day of s.c. Lassa virus inoculation (day 0) and again on days 3 and 6. Monkeys that received undiluted plasma (LNI = 4.1) (1 ml/kg per treatment) survived a lethal viral dose; those given a 1:3 dilution (LNI = 2.6) of this same plasma (1 ml/kg per treatment) died. Protection was restored when the volume of the 1:3 plasma dilution was increased to 3 ml/kg per treatment. Plasma diluted .gtoreq. 1:9 (LNI = .ltoreq. 1.5) delayed onset and suppressed the magnitude of viremia but failed to confer protection at 3 ml/kg per treatment. Immunological enhancement, defined as increased viremia or accelerated death, did not occur following inadequate treatment. Human convalescent plasma also protected recipient monkeys; reductions in mortality and viremia were accurately predicted by the LNI of the plasma. Plasma of Liberian origin neutralized a Liberian Lassa strain more effectively than a Sierra Leone strain in vitro (LNI = 2.8 and 1.6, respectively) and protected monkeys were effectively against the Liberian strain. Geographic origin is thus a factor in the selection of optimal plasma for treatment of human Lassa fever, since geographically matched plasma is more likely to contain adequate LNI titers against homologous Lassa virus strains. Early infusion of high-LNI plasma appears to be critical for treatment success.