Alexandra A Abu-Shmais, Rose J Miller, Alexis K Janke, Rachael M Wolters, Clinton M Holt, Nagarajan Raju, Robert H Carnahan, James E Crowe, Jarrod J Mousa, Ivelin S Georgiev
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引用次数: 0
摘要
人副流感病毒 3(HPIV3)是一种广泛传播的病原体,可在高危人群中引起严重的致命性呼吸道疾病。有效的应对措施正处于不同的开发阶段;然而,目前还没有获得许可的治疗和预防方案。融合糖蛋白(HPIV3 F)负责促进病毒进入宿主细胞,是抑制感染的中和抗体的主要靶标。虽然迄今为止已经发现了几种针对少量 HPIV3 F 表位的中和抗体,但与流感病毒和 SARS-CoV-2 等其他病原体相比,人们对 HPIV3 的抗体反应知之甚少。在本研究中,我们的目的是鉴定一组在多人中鉴定出的 HPIV3 特异性抗体的基因特征、表位特异性、中和潜力和公共性。我们鉴定出了 12 种针对 HPIV3 F 上三个不重叠表位的强效中和抗体,其中从两个不同个体中鉴定出的 6 种抗体使用了 Ig 重变异基因 IGHV 5-51,6 种抗体中有 5 种针对相同的表位。然而,尽管使用了相同的 H 链可变基因(VH),这些抗体却使用了多个不同的 L 链可变基因(VL)和不同的 H 链 CDR 3(CDRH3)序列。总之,这些结果提供了有关 HPIV3 中和抗体基因和功能特征的进一步信息,并表明存在一种与 VL 和 CDRH3 杂合性相关的可重复的 VH 依赖性抗体反应。了解 HPIV3 F 易感位点以及针对这些位点的抗体的基因和分子特征将有助于指导有效疫苗和疗法的开发工作。
Potent HPIV3-neutralizing IGHV5-51 Antibodies Identified from Multiple Individuals Show L Chain and CDRH3 Promiscuity.
Human parainfluenza virus 3 (HPIV3) is a widespread pathogen causing severe and lethal respiratory illness in at-risk populations. Effective countermeasures are in various stages of development; however, licensed therapeutic and prophylactic options are not available. The fusion glycoprotein (HPIV3 F), responsible for facilitating viral entry into host cells, is a major target of neutralizing Abs that inhibit infection. Although several neutralizing Abs against a small number of HPIV3 F epitopes have been identified to date, relatively little is known about the Ab response to HPIV3 compared with other pathogens, such as influenza virus and SARS-CoV-2. In this study, we aimed to characterize a set of HPIV3-specific Abs identified in multiple individuals for genetic signatures, epitope specificity, neutralization potential, and publicness. We identified 12 potently neutralizing Abs targeting three nonoverlapping epitopes on HPIV3 F. Among these, six Abs identified from two different individuals used Ig heavy variable gene IGHV 5-51, with five of the six Abs targeting the same epitope. However, despite the use of the same H chain variable (VH) gene, these Abs used multiple different L chain variable genes (VL) and diverse H chain CDR 3 (CDRH3) sequences. Together, these results provide further information about the genetic and functional characteristics of HPIV3-neutralizing Abs and suggest the existence of a reproducible VH-dependent Ab response associated with VL and CDRH3 promiscuity. Understanding sites of HPIV3 F vulnerability and the genetic and molecular characteristics of Abs targeting these sites will help guide efforts for effective vaccine and therapeutic development.
期刊介绍:
The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)