Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans.
Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans.
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DOI：
10.1371/journal.ppat.1009330
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发表时间：
2021-03
期刊：
影响因子：
6.7
通讯作者：
Tchilian E
中科院分区：
文献类型：
--
作者：
Holzer B;Rijal P;McNee A;Paudyal B;Martini V;Clark B;Manjegowda T;Salguero FJ;Bessell E;Schwartz JC;Moffat K;Pedrera M;Graham SP;Noble A;Bonnet-Di Placido M;La Ragione RM;Mwangi W;Beverley P;McCauley JW;Daniels RS;Hammond JA;Townsend AR;Tchilian E
猪是与人类相同的甲型流感病毒亚型的天然宿主，并与病毒进化密切相关，在两个方向上都有频繁的种间传播。2009年H1N1大流行病毒的出现说明了猪在人畜共患病毒株进化中的重要性。在这里，我们从H1N1pdm09感染的猪中产生了猪流感特异性单克隆抗体（mAb）。mAb识别人类靶向的相同的两个主要免疫显性血凝素（HA）表位，其中一个不被感染后雪貂抗血清识别，后者通常用于监测病毒进化。猪mAb的中和活性与有效的人抗HA mAb相当。此外，在H1N1pdm09攻击后，对猪预防性施用选定的猪mAb消除了肺病毒载量并大大降低了肺病理学，但没有消除病毒的鼻脱落。因此，来自猪的靶向HA的mAb可以显著降低疾病的严重程度。这些结果，加上猪和人的可比大小，表明猪是一个有价值的模型，了解如何最好地应用单克隆抗体作为治疗人类和监测流感病毒在人类的抗原漂移，从而提供信息高度相关的流感疫苗的建议。抗体（Ab）越来越多地用于治疗人类感染性疾病。猪是大型动物，是流感病毒的天然宿主，与人类非常相似。我们从流感感染的猪中产生了单克隆抗体，并表明它们识别与人类相同的病毒位点。其中一个位点没有被雪貂抗血清识别，而雪貂抗血清通常用于预测病毒的进化并为疫苗设计提供信息。我们还表明，预防性给予这些mAb之一的猪废除肺病毒载量和预防肺损伤感染流感。我们的结论是，猪是一个有用的模型，以测试如何最好地使用抗体治疗，并告知疫苗的建议，为人类。
Pigs are natural hosts for the same subtypes of influenza A viruses as humans and integrally involved in virus evolution with frequent interspecies transmissions in both directions. The emergence of the 2009 pandemic H1N1 virus illustrates the importance of pigs in evolution of zoonotic strains. Here we generated pig influenza-specific monoclonal antibodies (mAbs) from H1N1pdm09 infected pigs. The mAbs recognized the same two major immunodominant haemagglutinin (HA) epitopes targeted by humans, one of which is not recognized by post-infection ferret antisera that are commonly used to monitor virus evolution. Neutralizing activity of the pig mAbs was comparable to that of potent human anti-HA mAbs. Further, prophylactic administration of a selected porcine mAb to pigs abolished lung viral load and greatly reduced lung pathology but did not eliminate nasal shedding of virus after H1N1pdm09 challenge. Hence mAbs from pigs, which target HA can significantly reduce disease severity. These results, together with the comparable sizes of pigs and humans, indicate that the pig is a valuable model for understanding how best to apply mAbs as therapy in humans and for monitoring antigenic drift of influenza viruses in humans, thereby providing information highly relevant to making influenza vaccine recommendations. Antibodies (Ab) are increasingly used to treat human infectious diseases. Pigs are large animals, natural hosts for influenza viruses and very similar to humans. We generated monoclonal Abs from influenza infected pigs and show that they recognize the same sites of the virus as humans. One of these sites was not recognized by ferret anti-sera, which are commonly used to predict the evolution of the virus and inform vaccine design. We also show that prophylactic administration of one of these mAb to pigs abolished lung viral load and prevented lung damage following infection with influenza. We conclude that the pig is a useful model to test how best to use Abs for therapy and to inform vaccine recommendations for humans.
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