Abstract：
This longitudinal prospective controlled multicenter study aimed to monitor immunity generated by three exposures caused by breakthrough infections (BTI) after COVID-19-vaccination considering pre-existing cell-mediated immunity to common-corona-viruses (CoV) which may impact cellular reactivity against SARS-CoV-2. Anti-SARS-CoV-2-spike-IgG antibodies (anti-S-IgG) and cellular reactivity against Spike-(S)- and nucleocapsid-(N)-proteins were determined in fully-vaccinated (F) individuals who either experienced BTI (F+BTI) or had booster vaccination (F+Booster) compared to partially vaccinated (P+BTI) and unvaccinated (U) from 1 to 24 weeks post PCR-confirmed infection. High avidity anti-S-IgG were found in F+BTI compared to U, the latter exhibiting increased long-lasting pro-inflammatory cytokines to S-stimulation. CoV was associated with higher cellular reactivity in U, whereas no association was seen in F. The study illustrates the induction of significant S-specific cellular responses in F+BTI building-up basic immunity by three exposures. Only U seem to benefit from pre-existing CoV immunity but demonstrated inflammatory immune responses compared to F+BTI who immunologically benefit from enhanced humoral and cellular immunity after BTI. This study demonstrates that individuals with hybrid immunity from COVID-19-vaccination and BTI acquire a stable humoral and cellular immune response that is maintained for at least 6 months. Our findings corroborate recommendations by health authorities to build on basic immunity by three S-protein exposures.
摘要：
这项纵向前瞻性对照多中心研究旨在监测COVID-19疫苗接种后突破性感染（BTI）引起的三种暴露所产生的免疫力，考虑到预先存在的对普通冠状病毒（CoV）的细胞介导免疫力，这可能会影响细胞对SARS-CoV-2的反应性。在完全接种疫苗的（F）个体中确定了抗SARS-CoV-2-尖峰IgG抗体（抗S-IgG）和针对尖峰蛋白（S）-和核衣壳蛋白（N）蛋白的细胞反应性PCR确认感染后1至24周，与部分接种疫苗（PBTI）和未接种疫苗（U）相比，经历了BTI（FBTI）或加强疫苗接种（FBooster）。与U相比，在F+BTI中发现了高亲和力抗S-IgG，后者表现出增加的持久促炎细胞因子对S-刺激。CoV在U中与较高的细胞反应性相关，而在F中没有发现相关性。该研究表明，在FBTI中，通过三种暴露可诱导显着的S特异性细胞反应，从而建立基本免疫。只有U似乎受益于预先存在的CoV免疫,但与在BTI后从增强的体液和细胞免疫免疫中免疫受益的F+BTI相比,显示了炎性免疫应答。这项研究表明，具有来自COVID-19疫苗接种和BTI的混合免疫的个体获得了稳定的体液和细胞免疫应答，并维持了至少6个月。我们的发现证实了卫生当局通过三种S蛋白暴露来建立基本免疫力的建议。
