Department of Immunology and Microbiology, Centre for Medical Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Immun Inflamm Dis. 2023 Jun;11(6):e910. doi: 10.1002/iid3.910.
The development of vaccine candidates for COVID-19, and the administration of booster vaccines, has meant a significant reduction in COVID-19 related deaths world-wide and the easing of global restrictions. However, new variants of SARS-CoV-2 have emerged with less susceptibility to vaccine induced immunity leading to breakthrough infections among vaccinated people. It is generally acknowledged that immunoglobulins play the major role in immune-protection, primarily through binding to the SARS-COV-2 receptor binding domain (RBD) and thereby inhibiting viral binding to the ACE2 receptor. However, there are limited investigations of anti-RBD isotypes (IgM, IgG, IgA) and IgG subclasses (IgG1-4) over the course of vaccination and breakthrough infection.
In this study, SARS-CoV-2 humoral immunity is examined in a single subject with unique longitudinal sampling. Over a two year period, the subject received three doses of vaccine, had two active breakthrough infections and 22 blood samples collected. Serological testing included anti-nucleocapsid total antibodies, anti-RBD total antibodies, IgG, IgA, IgM and IgG subclasses, neutralization and ACE2 inhibition against the wildtype (WT), Delta and Omicron variants.
Vaccination and breakthrough infections induced IgG, specifically IgG1 and IgG4 as well as IgM and IgA. IgG1 and IgG4 responses were cross reactive and associated with broad inhibition.
The findings here provide novel insights into humoral immune response characteristics associated with SARS-CoV-2 breakthrough infections.
COVID-19 疫苗候选物的开发和加强疫苗的接种，意味着全球范围内与 COVID-19 相关的死亡人数显著减少，全球限制放宽。然而，SARS-CoV-2 的新变体出现，对疫苗诱导的免疫的敏感性降低，导致接种人群中出现突破性感染。人们普遍认为，免疫球蛋白在免疫保护中起着主要作用，主要通过与 SARS-COV-2 受体结合域（RBD）结合，从而抑制病毒与 ACE2 受体的结合。然而，在接种和突破性感染过程中，针对 RBD 的同种型（IgM、IgG、IgA）和 IgG 亚类（IgG1-4）的研究有限。
在这项研究中，对一个具有独特纵向采样的单一个体的 SARS-CoV-2 体液免疫进行了检查。在两年的时间里，该个体接受了三剂疫苗接种，经历了两次突破性感染和 22 次采血。血清学检测包括抗核衣壳总抗体、抗 RBD 总抗体、IgG、IgA、IgM 和 IgG 亚类、针对野生型（WT）、Delta 和 Omicron 变体的中和和 ACE2 抑制。
疫苗接种和突破性感染诱导了 IgG，特别是 IgG1 和 IgG4 以及 IgM 和 IgA。IgG1 和 IgG4 反应具有交叉反应性，并与广泛的抑制作用相关。
这些发现为 SARS-CoV-2 突破性感染相关的体液免疫反应特征提供了新的见解。
