SARS-CoV-2 疫苗接种使既往 SARS-CoV-2 感染患者的 CD4+ 刺突反应性 T 细胞库多样化。
SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection.
机构信息
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
出版信息
EBioMedicine. 2022 Jun;80:104048. doi: 10.1016/j.ebiom.2022.104048. Epub 2022 May 6.
BACKGROUND
COVID-19 mRNA vaccines elicit strong T and B cell responses to the SARS-CoV-2 spike glycoprotein in both SARS-CoV-2 naïve and experienced patients. However, it is unknown whether the post-vaccine CD4+ T cell responses seen in patients with a history of COVID-19 are due to restimulation of T cell clonotypes that were first activated during natural infection or if they are the result of new clones activated by the vaccine.
METHODS
To address this question, we analyzed the SARS-CoV-2 spike glycoprotein-specific CD4+ T cell receptor repertoire before and after vaccination in 10 COVID-19 convalescent patients and 4 SARS-CoV-2 naïve healthy donor vaccine recipients. We used the viral Functional Expansion of Specific T cells (ViraFEST) assay to quantitatively identify specific SARS-CoV-2 and common cold coronavirus CD4+ T cell clonotypes post COVID-19 disease resolution and post mRNA SARS-CoV-2 vaccination.
FINDINGS
We found that while some preexisting T cell receptor clonotypes persisted, the post-vaccine repertoire consisted mainly of vaccine-induced clones and was largely distinct from the repertoire induced by natural infection. Vaccination-induced clones led to an overall maintenance of the total number of SARS-CoV-2 reactive clonotypes over time through expansion of novel clonotypes only stimulated through vaccination. Additionally, we demonstrated that the vaccine preferentially induces T cells that are only specific for SARS-CoV-2 antigens, rather than T cells that cross-recognize SARS-CoV-2/common cold coronaviruses.
INTERPRETATION
These data demonstrate that SARS-CoV-2 vaccination in patients with prior SARS-CoV-2 infection induces a new antigen-specific repertoire and sheds light on the differential immune responses induced by vaccination versus natural infection.
FUNDING
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, The Johns Hopkins University, The Bill and Melinda Gates Foundation, NCI U54CA260492, NIH.
背景
COVID-19 mRNA 疫苗在 SARS-CoV-2 感染初治和既往感染患者中均能诱导强烈的针对 SARS-CoV-2 刺突糖蛋白的 T 细胞和 B 细胞应答。然而，尚不清楚既往 COVID-19 患者的疫苗后 CD4+T 细胞应答是由于最初在自然感染过程中被激活的 T 细胞克隆型的再刺激，还是由于疫苗激活的新克隆型所致。
方法
为解决这一问题，我们分析了 10 例 COVID-19 恢复期患者和 4 例 SARS-CoV-2 感染初治健康供者疫苗接种者接种疫苗前后 SARS-CoV-2 刺突糖蛋白特异性 CD4+T 细胞受体库。我们使用病毒特异性 T 细胞功能扩增（ViraFEST）测定法，在 COVID-19 疾病缓解后和 mRNA SARS-CoV-2 接种后定量鉴定 SARS-CoV-2 和普通感冒冠状病毒 CD4+T 细胞克隆型。
发现
我们发现，虽然一些预先存在的 T 细胞受体克隆型持续存在，但疫苗接种后的受体库主要由疫苗诱导的克隆型组成，且与自然感染诱导的受体库有很大不同。疫苗接种诱导的克隆型通过仅由疫苗刺激的新克隆型的扩增，导致 SARS-CoV-2 反应性克隆型的总数随时间推移而得到总体维持。此外，我们证明疫苗优先诱导仅特异性识别 SARS-CoV-2 抗原的 T 细胞，而不是交叉识别 SARS-CoV-2/普通感冒冠状病毒的 T 细胞。
结论
这些数据表明，在既往 SARS-CoV-2 感染患者中接种 SARS-CoV-2 疫苗会诱导新的抗原特异性受体库，并阐明了疫苗接种与自然感染诱导的免疫反应的差异。
资助
彭博∼金梅尔癌症免疫治疗研究所、约翰霍普金斯大学、比尔及梅琳达·盖茨基金会、NCI U54CA260492、NIH。
Zotero 插件