Nielsen Stine Sf, Vibholm Line K, Monrad Ida, Olesen Rikke, Frattari Giacomo S, Pahus Marie H, Højen Jesper F, Gunst Jesper D, Erikstrup Christian, Holleufer Andreas, Hartmann Rune, Østergaard Lars, Søgaard Ole S, Schleimann Mariane H, Tolstrup Martin
Department of Infectious Diseases, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
Department of Infectious Diseases, Aarhus University Hospital, Denmark.
EBioMedicine. 2021 Jun;68:103410. doi: 10.1016/j.ebiom.2021.103410. Epub 2021 Jun 4.
The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search and evaluation of new treatment modalities and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed.
We included 203 recovered SARS-CoV-2 infected patients in Denmark between April 3 and July 9 2020, at least 14 days after COVID-19 symptom recovery. The participants had experienced a range of disease severities from asymptomatic to severe. We collected plasma, serum and PBMC's for analysis of SARS-CoV-2 specific antibody response by Meso Scale analysis including other coronavirus strains, ACE2 competition, IgA ELISA, pseudovirus neutralization capacity, and dextramer flow cytometry analysis of CD8 T cells. The immunological outcomes were compared amongst severity groups within the cohort, and 10 pre-pandemic SARS-CoV-2 negative controls.
We report broad serological profiles within the cohort, detecting antibody binding to other human coronaviruses. 202(>99%) participants had SARS-CoV-2 specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 193(95%) individuals. A significant positive correlation (r=0.7804) between spike-ACE2 blocking antibody titers and neutralization potency was observed. Further, SARS-CoV-2 specific CD8 T-cell responses were clear and quantifiable in 95 of 106(90%) HLA-A2 individuals.
The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8 T-cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of their disease severity.
This study was supported by the Danish Ministry for Research and Education (grant# 0238-00001B) and The Danish Innovation Fund (grant# 0208-00018B).
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行目前在全球肆虐。为了解SARS-CoV-2感染的免疫特征，并有助于新治疗方法和疫苗的研究与评估，需要对针对SARS-CoV-2的适应性免疫反应进行全面表征。
我们纳入了2020年4月3日至7月9日期间丹麦203例康复的SARS-CoV-2感染患者，这些患者在新型冠状病毒肺炎（COVID-19）症状恢复后至少14天。参与者经历了从无症状到重症的一系列疾病严重程度。我们收集了血浆、血清和外周血单个核细胞（PBMC），通过中尺度分析来分析针对SARS-CoV-2的特异性抗体反应，包括其他冠状病毒株、血管紧张素转换酶2（ACE2）竞争、免疫球蛋白A（IgA）酶联免疫吸附测定（ELISA）、假病毒中和能力以及CD8 T细胞的四聚体流式细胞术分析。在队列中的严重程度组以及10例大流行前SARS-CoV-2阴性对照之间比较免疫结果。
我们报告了队列中的广泛血清学特征，检测到抗体与其他人类冠状病毒结合。202例（>99%）参与者具有SARS-CoV-2特异性抗体，193例（95%）个体观察到SARS-CoV-2中和以及刺突蛋白-ACE2受体相互作用阻断。观察到刺突蛋白-ACE2阻断抗体滴度与中和效力之间存在显著正相关（r=0.7804）。此外，在106例HLA-A2个体中的95例（90%）中，SARS-CoV-2特异性CD8 T细胞反应清晰且可量化。
病毒表面刺突蛋白被确定为中和抗体和CD8 T细胞反应的主要靶点。总体而言，大多数患者具有强大的适应性免疫反应，无论其疾病严重程度如何。
本研究由丹麦研究与教育部（资助编号：0238-00001B）和丹麦创新基金（资助编号：0208-00018B）资助。
