The Pirbright Institute, Pirbright, United Kingdom.
Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, United Kingdom.
PLoS Pathog. 2021 Mar 4;17(3):e1009330. doi: 10.1371/journal.ppat.1009330. eCollection 2021 Mar.
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.
猪是与人类相同亚型流感病毒的天然宿主,并且在两个方向上经常发生物种间的频繁传播,从而整合在病毒进化中。2009 年大流行性 H1N1 病毒的出现说明了猪在人畜共患病株进化中的重要性。在这里,我们从感染了 H1N1pdm09 的猪中产生了针对猪流感的单克隆抗体(mAbs)。这些 mAbs 识别了人类针对的两个主要免疫显性血凝素(HA)表位,其中一个表位不能被通常用于监测病毒进化的感染后雪貂抗血清识别。猪 mAbs 的中和活性可与强效的人类抗 HA mAbs 相媲美。此外,向猪预防性施用选定的猪 mAb 可消除肺部病毒载量并大大减轻肺部病理,但不能消除 H1N1pdm09 攻击后鼻病毒脱落。因此,针对 HA 的猪 mAbs 可显著降低疾病的严重程度。这些结果,再加上猪和人类的大小相当,表明猪是了解如何将 mAb 作为人类治疗方法以及监测人类流感病毒抗原漂移的有价值的模型,从而提供了与制定流感疫苗建议高度相关的信息。