Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period. Yu et al.

Understanding immune memory to Common Cold Coronaviruses (CCCs) impacts SARS-CoV-2 infection outcome, and is crucial for pan-corona vaccine development. With longitudinal pre-pandemic samples from 2016-2019, we assessed CCC-specific CD4+ T cell and antibody responses, comparing to other respiratory viruses and ubiquitous pathogens. CCC-specific memory CD4+ T cells were detected in most subjects, with comparable frequencies as other common antigens. Responses to CCC and other antigens sustained over time. CCC-specific CD4+ T cell responses were associated with low HLA-DR+CD38+ cell quantity and their magnitude did not correlate with yearly changes in CCC infection prevalence. Similarly, CCC-specific spike RBD-specific IgG responses were stable throughout the sampling period. Finally, high CCC-specific CD4+ T cell reactivity, but not antibody titers, was associated with pre-existing SARS-CoV-2 immunity. The results suggest a steady and sustained CCC responses, likely from a stable pool of memory CD4+ T cells, instead of fast decaying responses by frequent reinfections.阐明针对普通感冒冠状病毒（Common Cold Coronaviruses, CCCs）的免疫记忆，其可影响严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的感染结局，且对于广谱冠状病毒疫苗的研发至关重要。本研究依托2016至2019年的大流行前纵向样本，对普通感冒冠状病毒特异性CD4+ T细胞与抗体应答进行了检测分析，并将其与其他呼吸道病毒及普遍存在的病原体的应答进行了对比。多数受试者体内均可检测到普通感冒冠状病毒特异性记忆性CD4+ T细胞，其细胞频率与其他常见抗原诱导的应答水平相当。针对普通感冒冠状病毒与其他抗原的免疫应答可随时间持续存在。普通感冒冠状病毒特异性CD4+ T细胞应答与低水平的HLA-DR+CD38+细胞数量相关，且该应答的强度与普通感冒冠状病毒感染流行率的年度变化无显著相关性。类似地，普通感冒冠状病毒特异性刺突蛋白受体结合域（spike RBD）特异性IgG应答在整个采样周期内均保持稳定。最后，高水平的普通感冒冠状病毒特异性CD4+ T细胞反应性（而非抗体滴度）与预先存在的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）免疫状态显著相关。本研究结果表明，针对普通感冒冠状病毒的免疫应答呈现稳定且持续的特征，其大概率来源于稳定的记忆性CD4+ T细胞库，而非频繁再感染所诱导的快速衰减型应答。