Persistent immune imprinting after XBB.1.5 COVID vaccination in humans.
Persistent immune imprinting after XBB.1.5 COVID vaccination in humans.
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人类接种 XBB.1.5 COVID 疫苗后出现持续免疫印记。
DOI：
10.1101/2023.11.28.569129
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Veesler,David
中科院分区：
文献类型：
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作者：
Tortorici,MAlejandra;Addetia,Amin;Seo,AlbertJ;Brown,Jack;Sprouse,KaitlinR;Logue,Jenni;Clark,Erica;Franko,Nicholas;Chu,Helen;Veesler,David
免疫印记——也被称为“原始抗原原罪”——描述了首次接触病毒如何影响随后接触抗原相关毒株的免疫结果。研究表明，SARS-CoV-2 Omicron突破感染和二价COVID-19疫苗接种主要唤起先前用武汉-胡-1刺突接种mRNA诱导的交叉反应记忆B细胞和抗体，而不是启动识别Omicron特异性表位的初始B细胞。这些发现强调了反复暴露于武汉-胡-1病毒尖峰所造成的强烈免疫印记。为了了解免疫印迹是否可以克服，我们研究了注射更新版XBB.1.5 COVID mRNA疫苗增强剂后的记忆和血浆抗体反应。我们的数据显示，XBB.1.5增强剂引发了针对当前变体的中和抗体反应，这些变体主要是由先前由武汉- hu -1峰值诱导的预先存在的记忆B细胞的召回所主导。这些结果表明，即使通过疫苗接种和感染（包括XBB.1.5刺突增强mRNA接种后）多次暴露于Omicron刺突后，免疫印迹仍然存在，这将需要考虑指导未来疫苗增强剂的设计。
Immune imprinting - also known as ‘original antigenic sin’ - describes how the first exposure to a virus shapes the immunological outcome of subsequent exposures to antigenically related strains. SARS-CoV-2 Omicron breakthrough infections and bivalent COVID-19 vaccination were shown to primarily recall cross-reactive memory B cells and antibodies induced by prior mRNA vaccination with the Wuhan-Hu-1 spike rather than priming naive B cells that recognize Omicron-specific epitopes. These findings underscored a strong immune imprinting resulting from repeated Wuhan-Hu-1 spike exposures. To understand if immune imprinting can be overcome, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID mRNA vaccine booster. Our data show that the XBB.1.5 booster elicits neutralizing antibody responses against current variants that are dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. These results indicate that immune imprinting persists even after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 spike booster mRNA vaccination, which will need to be considered to guide the design of future vaccine boosters.