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动物源多克隆高免抗体的被动转移可保护小鼠免受致死性拉沙病毒感染。

Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection.

机构信息

Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

German Center for Infectious Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 20359 Hamburg, Germany.

出版信息

Viruses. 2023 Jun 26;15(7):1436. doi: 10.3390/v15071436.

Abstract

BACKGROUND

Lassa virus (LASV) can cause severe acute systemic infection in humans. No approved antiviral drugs or vaccines are currently available. Antibody-based therapeutics are considered a promising treatment strategy in the management of LASV disease.

METHODS

We used chimeric Ifnar C57BL/6 (Ifnar) mice, a lethal LASV mouse model, to evaluate the protective efficacy of polyclonal antibodies purified from sera of rabbits hyperimmunized with virus-like particles displaying native-like LASV glycoprotein GP spikes.

RESULTS

Polyclonal anti-LASV GP antibodies provided 100% protection against lethal LASV infection in a pre- and post-exposure treatment setting and prevented LASV disease. Treatment also significantly lowered viremia level and virus load in organs. When treatment was initiated at the onset of symptoms, the hyperimmune antibodies provided partial protection and increased the survival rate by 80%.

CONCLUSIONS

Our findings support the consideration of animal-derived hyperimmune antibodies targeting GP as an effective treatment option for highly pathogenic LASV.

摘要

背景

拉沙病毒(LASV)可引起人类严重的急性全身感染。目前尚无批准的抗病毒药物或疫苗。抗体为基础的治疗被认为是治疗 LASV 疾病的一种有前途的治疗策略。

方法

我们使用嵌合 Ifnar C57BL/6(Ifnar)小鼠,一种致死性 LASV 小鼠模型,来评估从经病毒样颗粒(展示天然样 LASV 糖蛋白 GP 刺突)高度免疫的兔血清中纯化的多克隆抗体的保护效力。

结果

多克隆抗 LASV GP 抗体在暴露前和暴露后治疗设置中提供了 100%的致死性 LASV 感染保护,并预防了 LASV 疾病。治疗还显著降低了病毒血症水平和器官中的病毒载量。当在症状出现时开始治疗时,高免疫抗体提供了部分保护,并将存活率提高了 80%。

结论

我们的发现支持考虑针对 GP 的动物源性高免疫抗体作为高度致病性 LASV 的有效治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa0/10384048/e8fefcfeeb6a/viruses-15-01436-g001.jpg

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