关键词: B cells COVID-19 vaccination Delta Omicron SARS-CoV-2 T cells breakthrough infection coronavirus de novo responses

Mesh : Humans SARS-CoV-2 / immunology COVID-19 / immunology virology Epitopes, T-Lymphocyte / immunology genetics CD8-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / immunology COVID-19 Vaccines / immunology Spike Glycoprotein, Coronavirus / immunology genetics Immunologic Memory / immunology Female Adult Male Mutation Middle Aged T-Lymphocytes / immunology Breakthrough Infections

来  源:   DOI:10.1016/j.xcrm.2024.101583   PDF(Pubmed)

Abstract:
Little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS2) vaccine breakthrough infections (BTIs) on the magnitude and breadth of the T cell repertoire after exposure to different variants. We studied samples from individuals who experienced symptomatic BTIs during Delta or Omicron waves. In the pre-BTI samples, 30% of the donors exhibited substantial immune memory against non-S (spike) SARS2 antigens, consistent with previous undiagnosed asymptomatic SARS2 infections. Following symptomatic BTI, we observed (1) enhanced S-specific CD4 and CD8 T cell responses in donors without previous asymptomatic infection, (2) expansion of CD4 and CD8 T cell responses to non-S targets (M, N, and nsps) independent of SARS2 variant, and (3) generation of novel epitopes recognizing variant-specific mutations. These variant-specific T cell responses accounted for 9%-15% of the total epitope repertoire. Overall, BTIs boost vaccine-induced immune responses by increasing the magnitude and by broadening the repertoire of T cell antigens and epitopes recognized.
摘要:
关于严重急性呼吸道综合症冠状病毒2(SARS-CoV-2或SARS2)疫苗突破感染(BTIs)对暴露于不同变体后T细胞库的大小和广度的影响知之甚少。我们研究了在Delta或Omicron波中经历过症状性BTI的个体的样本。在BTI之前的样本中,30%的供体表现出针对非S(尖峰)SARS2抗原的大量免疫记忆,与以前未诊断的无症状SARS2感染一致。在有症状的BTI之后,我们观察到(1)在没有先前无症状感染的供体中增强了S特异性CD4和CD8T细胞应答,(2)CD4和CD8T细胞对非S靶标的扩增反应(M,N,和nsps)独立于SARS2变体,和(3)识别变体特异性突变的新型表位的产生。这些变体特异性T细胞应答占总表位库的9%-15%。总的来说,BTIs通过增加T细胞抗原和识别的表位的数量和扩大其数量来增强疫苗诱导的免疫应答。
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