背景:COVID-19候选疫苗的开发以及加强疫苗的施用,这意味着全球范围内与COVID-19相关的死亡人数大幅减少,全球限制也有所放松。然而,SARS-CoV-2的新变种已经出现,对疫苗诱导的免疫的敏感性较低,导致接种疫苗的人群发生突破性感染。公认免疫球蛋白在免疫保护中起主要作用。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,抗RBD同种型的研究有限(IgM,IgG,在疫苗接种和突破性感染过程中,IgA)和IgG亚类(IgG1-4)。
方法:在本研究中,SARS-CoV-2体液免疫在单个受试者中进行了独特的纵向采样检查。在两年的时间里,受试者接受了三剂疫苗,有两个活跃的突破性感染和22个血液样本收集。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,中和和ACE2对野生型(WT)的抑制,Delta和Omicron变体。
结果:疫苗接种和突破性感染诱导IgG,特别是IgG1和IgG4以及IgM和IgA。IgG1和IgG4反应是交叉反应性的并且与广泛抑制相关。
结论:这里的发现提供了与SARS-CoV-2突破性感染相关的体液免疫应答特征的新见解。
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.