Immune memory determines infection risk and responses to future infections and vaccinations over potentially decades of life. Despite its centrality, the dynamics of memory to antigenically variable pathogens remains poorly understood. This Review examines how past exposures shape B cell responses to vaccinations with influenza and SARS-CoV-2. An overriding feature of vaccinations with these pathogens is the recall of primary responses, often termed ‘imprinting’ or ‘original antigenic sin’. These recalled responses can inhibit the generation of new responses unless some incompletely defined conditions are met. Depending on the context, immune memory can increase or decrease the total neutralizing antibody response to variant antigens, with apparent consequences for protection. These effects are easier to measure experimentally than epidemiologically, but there is evidence that both early and recent exposures influence vaccine effectiveness. A few immunological interactions between adaptive immune responses and antigens might explain the seemingly discrepant effects of memory. Overall, the complex observations point to a need for more quantitative approaches to integrate high-dimensional immune data from populations with diverse exposure histories. Such approaches could help identify optimal vaccination strategies against antigenically diverse pathogens.

免疫记忆决定了感染风险以及在可能几十年的生命中对未来感染和疫苗接种的反应。尽管它处于中心地位，但对抗原可变病原体的记忆动力学仍然知之甚少。本综述研究了过去的暴露如何影响 B 细胞对流感和 SARS-CoV-2 疫苗接种的反应。接种这些病原体疫苗的一个首要特征是回忆起原发性反应，通常被称为“印记”或“原始抗原罪”。这些召回的反应会抑制新反应的产生，除非满足一些不完全定义的条件。根据环境，免疫记忆可以增加或减少对变异抗原的总中和抗体反应，从而对保护产生明显的影响。这些影响更容易通过实验而不是流行病学来衡量，但有证据表明，早期和最近的暴露都会影响疫苗的有效性。适应性免疫反应和抗原之间的一些免疫相互作用可能解释了记忆看似不同的影响。总体而言，复杂的观察结果表明，需要更多的定量方法来整合来自不同暴露史的人群的高维免疫数据。这些方法可以帮助确定针对抗原性多样化病原体的最佳疫苗接种策略。