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重症新型冠状病毒肺炎患者会产生更高的特异性T细胞反应。

Severe SARS-CoV-2 patients develop a higher specific T-cell response.

作者信息

Demaret Julie, Lefèvre Guillaume, Vuotto Fanny, Trauet Jacques, Duhamel Alain, Labreuche Julien, Varlet Pauline, Dendooven Arnaud, Stabler Sarah, Gachet Benoit, Bauer Jules, Prevost Brigitte, Bocket Laurence, Alidjinou Enagnon Kazali, Lambert Marc, Yelnik Cécile, Meresse Bertrand, Dubuquoy Laurent, Launay David, Dubucquoi Sylvain, Montaigne David, Woitrain Eloise, Maggiotto François, Bou Saleh Mohamed, Top Isabelle, Elsermans Vincent, Jeanpierre Emmanuelle, Dupont Annabelle, Susen Sophie, Brousseau Thierry, Poissy Julien, Faure Karine, Labalette Myriam

机构信息

Institut d'Immunologie CHU de Lille Lille France.

U1286 - INFINITE - Institute for Translational Research in Inflammation Inserm CHU de Lille Univ. Lille Lille France.

出版信息

Clin Transl Immunology. 2020 Dec 23;9(12):e1217. doi: 10.1002/cti2.1217. eCollection 2020.

Abstract

OBJECTIVES

Assessment of the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for studying long-term immunity and vaccine strategies. We quantified IFNγ-secreting T cells reactive against the main viral SARS-CoV-2 antigens using a standardised enzyme-linked immunospot assay (ELISpot).

METHODS

Overlapping peptide pools built from the sequences of M, N and S viral proteins and a mix (MNS) were used as antigens. Using IFNγ T-CoV-Spot assay, we assessed T-cell and antibody responses in mild, moderate and severe SARS-CoV-2 patients and in control samples collected before the outbreak.

RESULTS

Specific T cells were assessed in 60 consecutive patients (mild,  = 26; moderate,  = 10; and severe patients,  = 24) during their follow-up (median time from symptom onset [interquartile range]: 36 days [28;53]). T cells against M, N and S peptide pools were detected in  = 60 (100%),  = 56 (93.3%),  = 55 patients (91.7%), respectively. Using the MNS mix, IFNγ T-CoV-Spot assay showed a specificity of 96.7% (95% CI, 88.5-99.6%) and a specificity of 90.3% (75.2-98.0%). The frequency of reactive T cells observed with M, S and MNS mix pools correlated with severity and with levels of anti-S1 and anti-RBD serum antibodies.

CONCLUSION

IFNγ T-CoV-Spot assay is a reliable method to explore specific T cells in large cohorts of patients. This test may become a useful tool to assess the long-lived memory T-cell response after vaccination. Our study demonstrates that SARS-CoV-2 patients developing a severe disease achieve a higher adaptive immune response.

摘要

目的

评估针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的适应性免疫反应对于研究长期免疫力和疫苗策略至关重要。我们使用标准化酶联免疫斑点试验(ELISpot)对针对主要SARS-CoV-2病毒抗原的分泌IFNγ的T细胞进行了定量。

方法

由M、N和S病毒蛋白序列构建的重叠肽库以及混合物(MNS)用作抗原。使用IFNγ T-CoV-Spot试验,我们评估了轻度、中度和重度SARS-CoV-2患者以及疫情爆发前收集的对照样本中的T细胞和抗体反应。

结果

在60例连续患者(轻度,n = 26;中度,n = 10;重度患者,n = 24)的随访期间(从症状发作开始的中位时间[四分位间距]:36天[28;53])评估了特异性T细胞。分别在n = 60(100%)、n = 56(93.3%)、n = 55例患者(91.7%)中检测到针对M、N和S肽库的T细胞。使用MNS混合物,IFNγ T-CoV-Spot试验显示特异性为96.7%(95%CI,88.5 - 99.6%),敏感性为90.3%(75.2 - 98.0%)。用M、S和MNS混合肽库观察到的反应性T细胞频率与疾病严重程度以及抗S1和抗RBD血清抗体水平相关。

结论

IFNγ T-CoV-Spot试验是在大量患者队列中探索特异性T细胞的可靠方法。该试验可能成为评估疫苗接种后长期记忆T细胞反应的有用工具。我们的研究表明,患严重疾病的SARS-CoV-2患者具有更高的适应性免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/7757425/b122c4bd3962/CTI2-9-e1217-g001.jpg

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