Aging and Viral Evolution Impair Immunity Against Dominant Pan-Coronavirus-Reactive T Cell Epitope

IF 3.7 3区 医学 Q2 IMMUNOLOGY
Lucie Loyal, Karsten Jürchott, Ulf Reimer, Lil Meyer-Arndt, Larissa Henze, Norbert Mages, Jak Kostrzanowski, Bernhard Reus, Maike Mangold, Beate Kruse, Manuela Dingeldey, Birgit Sawitzki, Janine Michel, Marica Grossegesse, Karsten Schnatbaum, Holger Wenschuh, Andreas Nitsche, Nils Lachmann, Bernd Timmermann, Claudia Giesecke-Thiel, Julian Braun, Florian Kern, Andreas Thiel
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Abstract

Immune evasion by escape mutations subverts immunity against SARS-CoV-2. A role of pan-coronavirus immunity for more durable protection is being discussed, but has remained understudied. We here investigated the effects of age, mutations, and homo-/heterologous vaccination regimens on the dominant pan-coronavirus-specific cellular and humoral epitope iCope after SARS-CoV-2 infection and vaccination in detail. In older individuals, the quantitatively and qualitatively reduced iCope-reactive CD4+ T cell responses with narrow TCR repertoires could not be enhanced by vaccination and were further compromised by emerging spike mutations. In contrast, pan-coronavirus-reactive humoral immunity was affected only by mutations and not by age. Our results reveal a distinct deficiency of the dichotomous layer of pan-coronavirus immunity in the older, critical for long-term protection against SARS-CoV-2 variants.

Abstract Image

衰老和病毒进化损害对显性泛冠状病毒反应性T细胞表位的免疫
逃避突变的免疫逃避破坏了对SARS-CoV-2的免疫。目前正在讨论泛冠状病毒免疫对更持久保护的作用,但仍未得到充分研究。我们在此详细研究了年龄、突变和同源/异源疫苗接种方案对SARS-CoV-2感染和接种后显性泛冠状病毒特异性细胞和体液表位iCope的影响。在老年人中,定量和定性降低的icope反应性CD4+ T细胞反应与狭窄的TCR库不能通过疫苗接种增强,并进一步受到新出现的刺突突变的损害。相比之下,泛冠状病毒反应性体液免疫仅受突变影响,而不受年龄影响。我们的研究结果显示,老年人明显缺乏泛冠状病毒免疫的二分类层,这对于长期保护免受SARS-CoV-2变体的侵害至关重要。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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