Center for Infectious Disease, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, Texas, USA
Center for Infectious Disease, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, Texas, USA.
mSphere. 2021 Mar 10;6(2):e00056-21. doi: 10.1128/mSphere.00056-21.
The concept of original antigenic sin (OAS) was put forth many years ago to explain how humoral memory responses generated against one set of antigens can affect the nature of antibody responses elicited to challenge infections or vaccinations containing a similar but not identical array of antigens. Here, we highlight the link between OAS and the germinal center reaction (GCR), a process unique to activated B cells undergoing somatic hypermutation and class switch recombination. It is the powerful response of activated memory B cells and the accompanying GCR that establish the foundations of OAS. We apply these concepts to the current COVID-19 pandemic and put forth several possible scenarios whereby OAS may result in either beneficial or harmful outcomes depending, hypothetically, on prior exposure to antigens shared between SARS-CoV-2 and seasonal human coronaviruses (hCoVs) that include betacoronaviruses (e.g., HCoV-OC43 and HCoV-HKU1) and alphacoronaviruses (e.g., HCoV-NL63 and HCoV-HKU1) (E. M. Anderson, E. C. Goodwin, A. Verma, C. P. Arevalo, et al., medRxiv, 2020, https://doi.org/10.1101/2020.11.06.20227215; S. M. Kissler, C. Tedijanto, E. Goldstein, Y. H. Grad, and M. Lipsitch, Science 368:860-868, 2020, https://doi.org/10.1126/science.abb5793).
抗原原始感染（OAS）的概念多年前被提出，用以解释针对一组抗原产生的体液记忆应答如何影响针对具有相似但不完全相同抗原谱的挑战感染或疫苗接种所引起的抗体应答的性质。在这里，我们强调了 OAS 与生发中心反应（GCR）之间的联系，这是一种独特的过程，仅发生在经历体细胞超突变和类别转换重组的活化 B 细胞中。正是活化记忆 B 细胞的强大应答以及伴随的 GCR 为 OAS 奠定了基础。我们将这些概念应用于当前的 COVID-19 大流行，并提出了几种可能的情况，根据假设，OAS 可能导致有益或有害的结果，这取决于 SARS-CoV-2 与季节性人类冠状病毒（hCoVs）之间共同抗原的先前暴露，包括β冠状病毒（例如，HCoV-OC43 和 HCoV-HKU1）和α冠状病毒（例如，HCoV-NL63 和 HCoV-HKU1）（E. M. Anderson, E. C. Goodwin, A. Verma, C. P. Arevalo, 等，medRxiv，2020，https://doi.org/10.1101/2020.11.06.20227215；S. M. Kissler, C. Tedijanto, E. Goldstein, Y. H. Grad, 和 M. Lipsitch，Science 368:860-868, 2020，https://doi.org/10.1126/science.abb5793）。
