Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
J Med Virol. 2023 Oct;95(10):e29122. doi: 10.1002/jmv.29122.
Despite recent advances in prophylactic vaccination, SARS-CoV-2 infections continue to cause significant morbidity. A better understanding of immune response differences between vaccinated individuals with and without later SARS-CoV-2 breakthrough infection is urgently needed. CoV-ADAPT is a prospective long-term study comparing humoral (anti-spike-RBD-IgG, neutralization capacity, avidity) and cellular (spike-induced T-cell interferon-γ [IFN-γ] release) immune responses in individuals vaccinated against SARS-CoV-2 at four different time points (three before and one after third vaccination). In this cohort study, 62 fully vaccinated individuals presented with SARS-CoV-2 breakthrough infections vs 151 without infection 3-7 months following third vaccination. Breakthrough infections significantly increased anti-spike-RBD-IgG (p < 0.01), but not spike-directed T-cell IFN-γ release (TC) or antibody avidity. Despite comparable surrogate neutralization indices, the functional neutralization capacity against SARS-CoV-2-assessed via a tissue culture-based assay-was significantly higher following breakthrough vs no breakthrough infection. Anti-spike-RBD-IgG and antibody avidity decreased with age (p < 0.01) and females showed higher anti-spike-RBD-IgG (p < 0.01), and a tendency towards higher antibody avidity (p = 0.051). The association between humoral and cellular immune responses previously reported at various time points was lost in subjects after breakthrough infections (p = 0.807). Finally, a machine-learning approach based on our large immunological dataset (a total of 49 variables) from different time points was unable to predict breakthrough infections (area under the curve: 0.55). In conclusion, distinct differences in humoral vs cellular immune responses in fully vaccinated individuals with or without breakthrough infection could be demonstrated. Breakthrough infections predominantly drive the humoral response without boosting the cellular component. Breakthrough infections could not be predicted based on immunological data, which indicates a superior role of environmental factors (e.g., virus exposure) in individualized risk assessment.
尽管最近在预防性疫苗接种方面取得了进展，但 SARS-CoV-2 感染仍会导致严重的发病率。迫切需要更好地了解接种疫苗的个体之间的免疫反应差异，这些个体有无随后的 SARS-CoV-2 突破性感染。CoV-ADAPT 是一项前瞻性长期研究，比较了在四个不同时间点（第三次接种前三次和第三次接种后一次）接种 SARS-CoV-2 疫苗的个体的体液（抗刺突-RBD-IgG、中和能力、亲和力）和细胞（刺突诱导的 T 细胞干扰素-γ [IFN-γ] 释放）免疫反应。在这项队列研究中，62 名完全接种疫苗的个体出现了 SARS-CoV-2 突破性感染，而 151 名个体在第三次接种后 3-7 个月没有感染。突破性感染显著增加了抗刺突-RBD-IgG（p<0.01），但没有增加针对刺突的 T 细胞 IFN-γ 释放（TC）或抗体亲和力。尽管替代中和指数相当，但通过基于组织培养的测定评估针对 SARS-CoV-2 的功能性中和能力在突破性感染后显著高于无突破性感染。抗刺突-RBD-IgG 和抗体亲和力随年龄增长而降低（p<0.01），女性的抗刺突-RBD-IgG 更高（p<0.01），并且抗体亲和力有更高的趋势（p=0.051）。在突破性感染后，先前在不同时间点报告的体液和细胞免疫反应之间的相关性丢失（p=0.807）。最后，基于我们来自不同时间点的大型免疫学数据集（总共 49 个变量）的机器学习方法无法预测突破性感染（曲线下面积：0.55）。总之，在有或没有突破性感染的完全接种疫苗的个体中，可以证明体液与细胞免疫反应存在明显差异。突破性感染主要驱动体液反应，而不会增强细胞成分。无法根据免疫学数据预测突破性感染，这表明环境因素（例如病毒暴露）在个体风险评估中起着重要作用。
Front Cell Infect Microbiol. 2024
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