Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures to antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA vaccination rather than priming Omicron-specific naive B cells. These findings indicate that immune imprinting occurs after repeated Wuhan-Hu-1 spike exposures, but whether it can be overcome remains unclear. To understand the persistence of immune imprinting, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID-19 mRNA vaccine booster. We showed that the XBB.1.5 booster elicited neutralizing antibody responses against current variants that were dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. Therefore, immune imprinting persists after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 booster vaccination, which will need to be considered to guide future vaccination.

中文翻译：

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人类接种 COVID-19 XBB.1.5 mRNA 增强剂后会出现持续免疫印记

免疫印记描述了第一次接触病毒如何影响随后接触抗原相关毒株的免疫结果。严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) Omicron 突破性感染和二价 COVID-19 疫苗接种主要召回由之前的 Wuu-Hu-1 刺突 mRNA 疫苗接种诱导的交叉反应记忆 B 细胞，而不是启动 Omicron 特异性初始 B 细胞细胞。这些发现表明，反复接触武汉-Hu-1尖峰后会出现免疫印记，但是否可以克服仍不清楚。为了了解免疫印记的持久性，我们研究了接种更新的 XBB.1.5 COVID-19 mRNA 疫苗加强剂后的记忆和血浆抗体反应。我们发现，XBB.1.5 加强剂引发了针对当前变体的中和抗体反应，这种反应主要是由武汉-Hu-1 尖峰诱导的先前存在的记忆 B 细胞的回忆引起的。因此，通过疫苗接种和感染多次暴露于 Omicron 峰值后，包括 XBB.1.5 加强疫苗接种后，免疫印记仍然存在，需要考虑这一点来指导未来的疫苗接种。