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基于肽的 COVID-19 T 细胞激活剂 CoVac-1 在健康成年人中的长期疗效。

Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults.

机构信息

Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany.

Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.

出版信息

Int J Infect Dis. 2024 Feb;139:69-77. doi: 10.1016/j.ijid.2023.11.009. Epub 2023 Nov 26.

Abstract

OBJECTIVES

T cell immunity is key for the control of viral infections including SARS-CoV-2, in particular with regard to immune memory and protection against arising genetic variants.

METHODS

We recently evaluated a peptide-based SARS-CoV-2 T cell activator termed CoVac-1 in a first-in-human trial in healthy adults. Here, we report on long-term safety and efficacy data of CoVac-1 until month 12.

RESULTS

CoVac-1 is well tolerated without long-term immune-related side effects and induces long-lasting anti-viral T cell responses in 100% of study participants, with potent expandability of clusters of differentiation (CD4) and CD8 T cells targeting multiple different CoVac-1 T cell epitopes. T cell responses were associated with stronger injection site reaction. Beyond induction of T cell immunity, 89% of subjects developed CoVac-1-specific immunoglobulin G antibodies which associated with the intensity of the T cell response, indicating that CoVac-1-specific CD4 T cells support the induction of B-cell responses. Vaccination with approved COVID-19 vaccines boosted CoVac-1-specific T cell responses. Overall, a low SARS-CoV-2 infection rate (8.3%) was observed.

CONCLUSION

Together, a single application of CoVac-1 elicits long-lived and broad SARS-CoV-2-specific T cell immunity, which further supports the current evaluation of our T cell activator in patients with congenital or acquired B-cell defects.

摘要

目的

T 细胞免疫对于控制包括 SARS-CoV-2 在内的病毒感染至关重要,尤其是在免疫记忆和预防出现遗传变异方面。

方法

我们最近在健康成年人中评估了一种名为 CoVac-1 的基于肽的 SARS-CoV-2 T 细胞激活剂,这是首次在人体试验中进行评估。在此,我们报告了 CoVac-1 的长期安全性和疗效数据,直至第 12 个月。

结果

CoVac-1 具有良好的耐受性,无长期免疫相关副作用,并在 100%的研究参与者中诱导持久的抗病毒 T 细胞反应,对多种不同的 CoVac-1 T 细胞表位具有强大的 CD4 和 CD8 T 细胞扩增能力。T 细胞反应与更强的注射部位反应相关。除了诱导 T 细胞免疫外,89%的受试者产生了 CoVac-1 特异性免疫球蛋白 G 抗体,这与 T 细胞反应的强度相关,表明 CoVac-1 特异性 CD4 T 细胞支持 B 细胞反应的诱导。接种已批准的 COVID-19 疫苗可增强 CoVac-1 特异性 T 细胞反应。总体而言,观察到 SARS-CoV-2 感染率较低(8.3%)。

结论

单次应用 CoVac-1 可引发持久且广泛的 SARS-CoV-2 特异性 T 细胞免疫,这进一步支持我们在先天性或获得性 B 细胞缺陷患者中对该 T 细胞激活剂的当前评估。

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