We review the phenomenon of “original antigenic sin” (OAS) in antibody responses to influenza A virus (IAV) infection or vaccination. OAS refers to the preferential induction of antibodies with higher affinity to priming versus boosting immunogens. We emphasize its mechanistic basis and origins in the basic immunobiology of B-cell responses to myriad immunogens. We tabulate 23 studies in animals and humans to show that the magnitude of OAS depends on many variables. We discuss a number of misconceptions about OAS, examine the extent to which OAS is sinful, and argue that OAS is evolutionary selected and not a deleterious by-product of selection for other features of the immune response. We end by raising questions regarding the mechanistic basis of OAS whose answers could contribute to improving influenza virus vaccines on the road to the holy grail of a “universal” influenza vaccine.

中文翻译：

---

原始抗原罪：多么原始？有罪吗？

我们回顾了对甲型流感病毒（IAV）感染或疫苗接种的抗体反应中的“原始抗原罪”（OAS）现象。OAS是指与引发免疫原相比增强对免疫原具有更高亲和力的抗体的优先诱导。我们强调其机制基础和起源于无数免疫原的B细胞反应的基本免疫生物学。我们对动物和人类的23项研究进行列表，以表明OAS的大小取决于许多变量。我们讨论了许多有关OAS的误解，研究了OAS有罪的程度，并认为OAS是进化选择的，而不是免疫应答其他特征选择的有害副产品。