疫苗诱导的免疫球蛋白G对严重急性呼吸系统综合征冠状病毒2型的高亲和力:与保护性体液免疫的潜在相关性

G. Bauer
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引用次数: 9

摘要

免疫球蛋白G (IgG)的亲和力是指其与靶抗原的结合强度。由于IgG反应的亲和成熟,贪婪也在成熟。因此,急性感染的特点是低贪婪的IgG,而过去的感染通常与高贪婪的IgG相关。贪婪成熟也被观察到作为最佳疫苗接种的结果。贪婪已被证明在许多微生物系统的保护性体液免疫中起重要作用。严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染后,情况与其他病毒感染不同,因为大多数感染病例所达到的中等程度的贪婪程度与仅接种一次疫苗所达到的程度相似。相比之下,在大多数接种疫苗的个体中,两个接种步骤导致针对病毒刺突蛋白S1 (S1)的IgG的亲和力高得多。因此,两个接种步骤似乎比自然感染允许更广泛的亲和力/亲和性成熟。两个接种步骤后的贪婪成熟程度是不均匀的。它可以通过第三步接种进一步加强。完全的贪婪成熟似乎依赖于成熟过程中抗原的持续可用性。值得关注的变异似乎增加了它们的受体结合域(RBD)对血管紧张素转换酶-2 (ACE2)的亲和力和/或降低了对中和抗体的敏感性。经典的中和试验并不一定反映中和IgG的快速性,因为它们从S1与ACE2的结合中解析S1与IgG之间的结合反应。这种方法减弱了IgG和ACE对S1 RBD的关键竞争反应。定量贪婪度测定可能是确定接种疫苗后仅具有次优保护性免疫的个体的必要工具,因此可能从额外的加强免疫中受益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
High avidity of vaccine-induced immunoglobulin G against SARS-CoV-2: potential relevance for protective humoral immunity
Avidity of immunoglobulin G (IgG) is defined as its binding strength to its target antigen. As a consequence of affinity maturation of the IgG response, avidity is maturing as well. Therefore, acute infections are characterized by low-avidity IgG, whereas past infections are usually associated with high-avidity IgG. Avidity maturation is also observed as a consequence of optimal vaccination. Avidity has been shown to play a significant role in protective humoral immunity in many microbial systems. After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation is different compared to other viral infections, as the moderate degree of avidity reached in most cases of infection is similar to that reached after only one vaccination step. In contrast, two vaccination steps lead to a much higher avidity of IgG directed towards viral spike protein S1 (S1) in the majority of vaccinated individuals. Therefore, it seems that two vaccination steps allow for a more extended affinity/avidity maturation than natural infection. The degree of avidity maturation after two vaccination steps is heterogeneous. It can be further enhanced by a third vaccination step. Complete avidity maturation seems to depend on sustained availability of antigen during the maturation process. Variants of concern seem to increase the affinity of their receptor-binding domain (RBD) to angiotensin-converting enzyme-2 (ACE2) and/or to decrease the susceptibility for neutralizing antibodies. Classical neutralization tests do not necessarily reflect the avidity of neutralizing IgG, as they operationally dissect the binding reaction between S1 and IgG from the binding of the S1 to ACE2. This approach fades out critical competition reactions between IgG and ACE for RBD of the S1. Quantitative avidity determination might be an essential tool to define individuals that only possess suboptimal protective immunity after vaccination and therefore might benefit from an additional booster immunization.
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