Key Points Neutralizing mAb 2–12C reduces influenza viral load and lung pathology in pigs. DNA plasmid–encoded 2–12C reduces lung pathology. The pig is a useful preclinical model for testing mAbs and mAb delivery platforms. 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.

中文翻译：

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建立用于评估单克隆抗体递送平台的猪流感攻击模型

要点 中和 mAb 2–12C 可降低猪的流感病毒载量和肺部病变。DNA 质粒编码的 2–12C 减少了肺部病变。猪是用于测试 mAb 和 mAb 递送平台的有用的临床前模型。单克隆抗体可能是疫苗接种和治疗流感病毒感染的药物的辅助手段。然而，小型动物模型能否准确预测人类疗效仍存在疑问。我们已经建立了猪，一种大型的流感天然宿主动物，与人类有许多生理相似之处，作为测试 mAb 的可靠模型。我们表明，在大流行性 H1N1 流感攻击后，以 15 mg/kg 的剂量预防性施用针对血凝素头部的强中和性 mAb (2–12C) 可减少病毒载量和肺部病理学。1 mg/kg 的较低剂量 2-12C 或 DNA 质粒编码的 2-12C 版本可减少肺部的病理和病毒载量，但不会减少鼻拭子中的病毒脱落。我们建议猪流感模型将有助于在人体试验之前测试候选 mAb 和新兴的递送平台。