Davis Samantha K, Selva Kevin John, Lopez Ester, Haycroft Ebene R, Lee Wen Shi, Wheatley Adam K, Juno Jennifer A, Adair Amy, Pymm Phillip, Redmond Samuel J, Gherardin Nicholas A, Godfrey Dale I, Tham Wai-Hong, Kent Stephen J, Chung Amy W
Department of Microbiology and Immunology The Peter Doherty Institute for Infection and Immunity University of Melbourne Melbourne VIC Australia.
The Walter and Eliza Hall Institute of Medical Research Melbourne VIC Australia.
Clin Transl Immunology. 2022 Oct 23;11(10):e1424. doi: 10.1002/cti2.1424. eCollection 2022.
Following infection with SARS-CoV-2, virus-specific antibodies are generated, which can both neutralise virions and clear infection via Fc effector functions. The importance of IgG antibodies for protection and control of SARS-CoV-2 has been extensively reported. By comparison, other antibody isotypes including IgA have been poorly characterised.
Here, we characterised plasma IgA from 41 early convalescent COVID-19 subjects for neutralisation and Fc effector functions.
Convalescent plasma IgA from > 60% of the cohort had the capacity to inhibit the interaction between wild-type RBD and ACE2. Furthermore, a third of the cohort induced stronger IgA-mediated ACE2 inhibition than matched IgG when tested at equivalent concentrations. Plasma IgA and IgG from this cohort broadly recognised similar RBD epitopes and had similar capacities to inhibit ACE2 from binding to 22 of the 23 prevalent RBD mutations assessed. However, plasma IgA was largely incapable of mediating antibody-dependent phagocytosis in comparison with plasma IgG.
Overall, convalescent plasma IgA contributed to the neutralising antibody response of wild-type SARS-CoV-2 RBD and various RBD mutations. However, this response displayed large heterogeneity and was less potent than IgG.
感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)后,会产生病毒特异性抗体,这些抗体既能中和病毒粒子,又能通过Fc效应功能清除感染。IgG抗体对SARS-CoV-2的保护和控制作用已得到广泛报道。相比之下,包括IgA在内的其他抗体亚型的特征了解较少。
在此,我们对41名早期康复的冠状病毒病2019(COVID-19)患者的血浆IgA进行了中和及Fc效应功能的特征分析。
超过60%的队列康复期血浆IgA有能力抑制野生型受体结合域(RBD)与血管紧张素转换酶2(ACE2)之间的相互作用。此外,当以等效浓度测试时,该队列中有三分之一的患者诱导的IgA介导的ACE2抑制作用比匹配的IgG更强。该队列的血浆IgA和IgG广泛识别相似的RBD表位,并且在抑制ACE2与所评估的23种流行RBD突变中的22种结合方面具有相似的能力。然而,与血浆IgG相比,血浆IgA在很大程度上无法介导抗体依赖性吞噬作用。
总体而言,康复期血浆IgA对野生型SARS-CoV-2 RBD和各种RBD突变的中和抗体反应有贡献。然而,这种反应表现出很大的异质性,且效力低于IgG。