The impact of initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOC) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection+two vaccine doses), S1 antibody, memory B cells and heterologous neutralization of B.1.351, P.1 and B.1.617.2 plateaued, while B.1.1.7 neutralization and spike T cell responses increased. Serology using Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over 5-months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.

中文翻译：

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异源感染和疫苗接种可形成针对 SARS-CoV-2 变种的免疫力


严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 初始感染株对下游异源相关变异 (VOC) 免疫的影响尚不清楚。通过研究纵向医护人员队列，我们​​发现在三次抗原暴露（感染+两剂疫苗）后，S1 抗体、记忆 B 细胞和 B.1.351、P.1 和 B.1.617.2 的异源中和趋于稳定，而 B. 1.1.7 中和和尖峰T细胞反应增加。使用武汉 Hu-1 刺突受体结合域的血清学结果很难预测针对 VOC 的中和免疫。针对 VOC 的中和效力随着异源病毒的接触和抗原暴露的次数而变化。从第二剂疫苗起 5 个月内，中和效力有所下降，具体取决于目标 VOC。感染和疫苗接种过程中遇到的尖峰异源组合形成了针对 VOC 的后续交叉保护，这对面向未来的下一代疫苗具有影响。