多年前提出了原始抗原sin(OAS)的概念,以解释针对一组抗原产生的体液记忆反应如何影响激发感染或疫苗的抗体反应的性质。这里,我们强调了OAS和生发中心反应(GCR)之间的联系,激活的B细胞经历体细胞超突变和类别转换重组所特有的过程。激活的记忆B细胞和伴随的GCR的强大反应建立了OAS的基础。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,根据这些情况,OAS可能会导致有益或有害的结果,假设,关于先前暴露于SARS-CoV-2和季节性人类冠状病毒(hCoV)之间共享的抗原,包括β冠状病毒(例如,HCoV-OC43和HCoV-HKU1)和α病毒(例如,HCoV-NL63和HCoV-HKU1)(E.M.安德森,E.C.古德温,A.Verma,C.P.阿雷瓦洛,etal.,medRxiv,2020,https://doi.org/10.1101/2020.11.06.20227215;S.M.Kissler,C.Tedijanto,E.Goldstein,Y.H.Grad,还有M.Lipsitch,科学368:860-868,2020,https://doi.org/10.1126/science。abb5793).
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).