Human CD4+ T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential,Clinical & Experimental Immunology

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Human CD4+ T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2021-06-01 , DOI: 10.1111/cei.13627
Johan Verhagen ₁ , Edith D van der Meijden ₁ , Vanessa Lang ₁ , Andreas E Kremer ₂ , Simon Völkl ₁ , Andreas Mackensen ₁ , Michael Aigner ₁ , Anita N Kremer ₁

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Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4⁺ T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4⁺ T cell therapy of COVID-19.

中文翻译：

具有治疗潜力的 SARS-CoV-2 刺突蛋白和核衣壳蛋白显性表位特异的人类 CD4+ T 细胞

自 2019 年 12 月以来，冠状病毒病 19 (COVID-19) 在世界各地迅速传播，导致全球努力开发疫苗和治疗方法。尽管取得了广泛进展，但仍然需要治疗来增强受感染的免疫功能低下个体的免疫反应，例如最近接受造血干细胞移植的癌症患者。针对 COVID-19 的免疫保护是由短暂的中和抗体和持久的病毒反应性 T 细胞介导的。因此，我们建议 T 细胞疗法可能会增强当前治疗的疗效。为了获得最大的疗效和最小的副作用，任何细胞疗法的设计都必须尽可能具体和有针对性，这一点很重要。在这里，我们鉴定了来自 COVID-19 患者的 T 细胞，这些 T 细胞对 SARS-CoV-2 病毒的两种主要抗原（刺突蛋白和核衣壳蛋白）具有潜在的保护性反应。通过生成高度病毒反应性 CD4 ⁺ T 细胞克隆，我们能够确认一组九个免疫显性表位，并表征针对这些表位的 T 细胞反应。因此，检查了 T 细胞克隆对其特定表位的敏感性，以及其细胞因子反应的程度和焦点。此外，使用先进的 T 细胞受体 (TCR) 测序方法，我们确定了感兴趣克隆的配对 TCR-αβ 序列。^{虽然这些关于有限人群的数据需要进一步扩展以实现普遍应用，但本文提出的结果构成了迈向 TCR 转基因 CD4 +} T 细胞疗法的 COVID-19 的关键第一步。

更新日期：2021-06-01

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