Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
Sci Transl Med. 2021 Jan 20;13(577). doi: 10.1126/scitranslmed.abf1555. Epub 2020 Dec 7.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), primarily infects cells at mucosal surfaces. Serum neutralizing antibody responses are variable and generally low in individuals that suffer mild forms of COVID-19. Although potent immunoglobulin G (IgG) antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might affect the initial viral spread and transmissibility from the mucosa. Here, we characterize the IgA response to SARS-CoV-2 in a cohort of 149 convalescent individuals after diagnosis with COVID-19. IgA responses in plasma generally correlated with IgG responses. Furthermore, clones of IgM-, IgG-, and IgA-producing B cells were derived from common progenitor cells. Plasma IgA monomers specific to SARS-CoV-2 proteins were demonstrated to be twofold less potent than IgG equivalents. However, IgA dimers, the primary form of antibody in the nasopharynx, were, on average, 15 times more potent than IgA monomers against the same target. Thus, dimeric IgA responses may be particularly valuable for protection against SARS-CoV-2 and for vaccine efficacy.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是导致 2019 年冠状病毒病(COVID-19)的病毒,主要感染黏膜表面的细胞。血清中和抗体反应在患有 COVID-19 轻症的个体中是多变的,通常较低。虽然有效的免疫球蛋白 G(IgG)抗体可以中和该病毒,但对于可能影响病毒从黏膜初始传播和传染性的分泌型抗体,如 IgA,了解较少。在这里,我们在 COVID-19 诊断后对 149 名康复个体的队列中,对 SARS-CoV-2 的 IgA 反应进行了表征。血浆中的 IgA 反应通常与 IgG 反应相关。此外,IgM、IgG 和 IgA 产生 B 细胞的克隆源自共同的祖细胞。证明针对 SARS-CoV-2 蛋白的血浆 IgA 单体比 IgG 等效物的效力低两倍。然而,针对同一靶标的 IgA 二聚体,平均比 IgA 单体的效力高 15 倍。因此,二聚体 IgA 反应可能对预防 SARS-CoV-2 和疫苗功效特别有价值。