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建立猪流感挑战模型评估单克隆抗体输送平台。

Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms.

机构信息

The Pirbright Institute, Pirbright GU24 0NF, United Kingdom.

Inovio Pharmaceuticals, San Diego, CA 92121.

出版信息

J Immunol. 2020 Aug 1;205(3):648-660. doi: 10.4049/jimmunol.2000429. Epub 2020 Jun 26.

Abstract

mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid-encoded version of 2-12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials.

摘要

单克隆抗体可能是流感病毒感染治疗中疫苗和药物的辅助手段。然而,目前仍存在一些问题,即小动物模型是否能准确预测其在人类中的疗效。我们已经建立了猪这种大型天然流感宿主动物的模型,其具有许多与人类相似的生理特性,可作为测试单克隆抗体的强大模型。我们发现,在大流行性 H1N1 流感病毒感染后,预防性给予 15mg/kg 的具有强中和作用的血凝素头部单克隆抗体(2-12C)可降低病毒载量和肺部病理学损伤。1mg/kg 的低剂量 2-12C 或 2-12C 的 DNA 质粒编码版本可降低肺部的病理学和病毒载量,但不能降低鼻拭子中的病毒脱落。我们提出,猪流感模型将有助于在人类试验之前测试候选单克隆抗体和新兴的给药平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd5/7372317/fc5e5c66341c/ji2000429f1.jpg

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