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一种非中和抗体通过与效应细胞相互作用广泛保护机体免受流感病毒感染。

A non-neutralizing antibody broadly protects against influenza virus infection by engaging effector cells.

机构信息

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

出版信息

PLoS Pathog. 2021 Aug 5;17(8):e1009724. doi: 10.1371/journal.ppat.1009724. eCollection 2021 Aug.

DOI:10.1371/journal.ppat.1009724
PMID:34352041
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8341508/
Abstract

Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HAmg) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HAfg) during lethal dose challenge. We employed a single B-cell screening platform to isolate the cross-protective monoclonal antibody (mAb) 651 from mice immunized with the HAmg of A/Brisbane/59/2007 (H1N1) influenza virus (Bris/07). The mAb 651 recognized the head domain of a broad spectrum of HAs from groups 1 and 2 influenza A viruses and offered prophylactic and therapeutic efficacy against A/California/07/2009 (H1N1) (Cal/09) and Bris/07 infections in mice. The antibody did not possess neutralizing activity; however, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis mediated by natural killer cells and alveolar macrophages were important in the protective efficacy of mAb 651. Together, this study highlighted the significance of effector functions for non-neutralizing antibodies to exhibit protection against influenza virus infection.

摘要

血凝素 (HA) 是流感病毒的免疫优势蛋白。我们之前的研究表明，与注射完全糖基化 HA (HAfg) 的小鼠相比，注射单糖基化流感 A HA (HAmg) 的小鼠在致死剂量攻毒时产生了交叉株反应性抗体，并且得到了更好的保护。我们采用单 B 细胞筛选平台，从接种了 A/Brisbane/59/2007 (H1N1) 流感病毒 (Bris/07) 的 HAmg 的小鼠中分离出了具有交叉保护作用的单克隆抗体 (mAb) 651。mAb 651 识别了来自 1 型和 2 型流感 A 病毒的广泛 HA 的头部结构域，并在小鼠中对 A/California/07/2009 (H1N1) (Cal/09) 和 Bris/07 感染提供了预防和治疗效果。该抗体没有中和活性；然而，自然杀伤细胞和肺泡巨噬细胞介导的抗体依赖的细胞细胞毒性和抗体依赖的细胞吞噬作用对于 mAb 651 的保护效果很重要。综上所述，本研究强调了效应功能对于非中和性抗体发挥保护作用以抵御流感病毒感染的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/31c3b038c607/ppat.1009724.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/e1e88eb9bc98/ppat.1009724.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/a08b191a3a0f/ppat.1009724.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/d7b784e389dc/ppat.1009724.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/84787b60562f/ppat.1009724.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/31c3b038c607/ppat.1009724.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/e1e88eb9bc98/ppat.1009724.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/a08b191a3a0f/ppat.1009724.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/d7b784e389dc/ppat.1009724.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/84787b60562f/ppat.1009724.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6529/8341508/31c3b038c607/ppat.1009724.g005.jpg

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