J Clin Invest. 2023 Jan 3;133(1):e162192. doi: 10.1172/JCI162192.
Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccinations targeting the spike protein (S) offer protective immunity against coronavirus disease 2019 (COVID-19). This immunity may further be shaped by cross-reactivity with common cold coronaviruses. Mutations arising in S that are associated with altered intrinsic virus properties and immune escape result in the continued circulation of SARS-CoV-2 variants. Potentially, vaccine updates will be required to protect against future variants of concern, as for influenza. To offer potent protection against future variants, these second-generation vaccines may need to redirect immunity to epitopes associated with immune escape and not merely boost immunity toward conserved domains in preimmune individuals. For influenza, efficacy of repeated vaccination is hampered by original antigenic sin, an attribute of immune memory that leads to greater induction of antibodies specific to the first-encountered variant of an immunogen compared with subsequent variants. In this Review, recent findings on original antigenic sin are discussed in the context of SARS-CoV-2 evolution. Unanswered questions and future directions are highlighted, with an emphasis on the impact on disease outcome and vaccine design.
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的感染和针对刺突蛋白 (S) 的疫苗接种提供了针对 2019 年冠状病毒病 (COVID-19) 的保护性免疫。这种免疫可能进一步受到与普通感冒冠状病毒交叉反应的影响。S 中与内在病毒特性改变和免疫逃逸相关的突变导致 SARS-CoV-2 变体的持续传播。可能需要更新疫苗以预防未来令人关注的变体，就像预防流感一样。为了提供针对未来变体的有效保护，这些第二代疫苗可能需要将免疫重定向到与免疫逃逸相关的表位，而不仅仅是针对预先免疫个体中的保守结构域来增强免疫。对于流感，由于原始抗原性错误，重复接种疫苗的效果受到阻碍，这是免疫记忆的一个属性，导致与随后的变体相比，对初次遇到的免疫原的变体更特异性地诱导抗体。在这篇综述中，讨论了 SARS-CoV-2 进化背景下的原始抗原性错误的最新发现。强调了未解决的问题和未来的方向，重点是对疾病结果和疫苗设计的影响。
