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不同 COVID-19 疫苗接种方案后产生的持久的刺突特异性 T 细胞反应,不会因加强针接种而进一步增强。

Durable spike-specific T cell responses after different COVID-19 vaccination regimens are not further enhanced by booster vaccination.

机构信息

Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.

Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.

出版信息

Sci Immunol. 2022 Dec 23;7(78):eadd3899. doi: 10.1126/sciimmunol.add3899. Epub 2022 Nov 1.

Abstract

Several COVID-19 vaccines are approved to prevent severe disease outcome after SARS-CoV-2 infection. Whereas induction and functionality of antiviral antibody response are largely studied, the induction of T cells upon vaccination with the different approved COVID-19 vaccines is less studied. Here, we report on T cell immunity 4 weeks and 6 months after different vaccination regimens and 4 weeks after an additional booster vaccination in comparison with SARS-CoV-2 T cell responses in convalescents and prepandemic donors using interferon-gamma ELISpot assays and flow cytometry. Increased T cell responses and cross-recognition of B.1.1.529 Omicron variant-specific mutations were observed ex vivo in mRNA- and heterologous-vaccinated donors compared with vector-vaccinated donors. Nevertheless, potent expandability of T cells targeting the spike protein was observed for all vaccination regimens, with frequency, diversity, and the ability to produce several cytokines of vaccine-induced T cell responses comparable with those in convalescent donors. T cell responses for all vaccinated donors significantly exceeded preexisting cross-reactive T cell responses in prepandemic donors. Booster vaccination led to a significant increase in anti-spike IgG responses, which showed a marked decline 6 months after complete vaccination. In contrast, T cell responses remained stable over time after complete vaccination with no significant effect of booster vaccination on T cell responses and cross-recognition of Omicron BA.1 and BA.2 mutations. This suggested that booster vaccination is of particular relevance for the amelioration of antibody response. Together, our work shows that different vaccination regimens induce broad and long-lasting spike-specific CD4 and CD8 T cell immunity to SARS-CoV-2.

摘要

几种 COVID-19 疫苗已被批准用于预防 SARS-CoV-2 感染后的重症疾病结局。虽然抗病毒抗体反应的诱导和功能得到了广泛研究,但不同批准的 COVID-19 疫苗接种后 T 细胞的诱导研究较少。在这里,我们使用干扰素-γ ELISpot assays 和流式细胞术报告了不同疫苗接种方案 4 周和 6 个月后以及与 SARS-CoV-2 恢复期和大流行前供体相比,在 4 周后再次接种加强针后的 T 细胞免疫。与载体疫苗接种者相比,mRNA 和异源疫苗接种者的 T 细胞反应在体外显示出更高的 T 细胞反应和对 B.1.1.529 奥密克戎变异特异性突变的交叉识别。然而,所有疫苗接种方案都观察到针对刺突蛋白的 T 细胞具有强大的扩增能力,疫苗诱导的 T 细胞反应的频率、多样性和产生多种细胞因子的能力与恢复期供体相当。所有接种疫苗的供体的 T 细胞反应明显超过大流行前供体中预先存在的交叉反应性 T 细胞反应。加强针接种导致针对刺突蛋白的抗 IgG 反应显著增加,而在完全接种疫苗 6 个月后,该反应明显下降。相比之下,T 细胞反应在完全接种疫苗后保持稳定,加强针接种对 T 细胞反应和对奥密克戎 BA.1 和 BA.2 突变的交叉识别没有显著影响。这表明加强针接种对于改善抗体反应特别重要。总之,我们的工作表明,不同的疫苗接种方案可诱导针对 SARS-CoV-2 的广泛且持久的刺突特异性 CD4 和 CD8 T 细胞免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e4d/9798886/7614cdf4ecbf/sciimmunol.add3899-f1.jpg

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