Loyal Lucie, Jürchott Karsten, Reimer Ulf, Meyer-Arndt Lil, Henze Larissa, Mages Norbert, Kostrzanowski Jak, Reus Bernhard, Mangold Maike, Kruse Beate, Dingeldey Manuela, Sawitzki Birgit, Michel Janine, Grossegesse Marica, Schnatbaum Karsten, Wenschuh Holger, Nitsche Andreas, Lachmann Nils, Timmermann Bernd, Giesecke-Thiel Claudia, Braun Julian, Kern Florian, Thiel Andreas
Si-M/"Der Simulierte Mensch" a science framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin, Berlin, Germany.
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Immunomics - Regenerative Immunology and Aging, Berlin, Germany.
Eur J Immunol. 2025 Jul;55(7):e51888. doi: 10.1002/eji.202551888.
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.
逃逸突变导致的免疫逃逸破坏了针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的免疫力。泛冠状病毒免疫在提供更持久保护方面的作用正在被讨论，但仍未得到充分研究。我们在此详细研究了年龄、突变以及同源/异源疫苗接种方案对SARS-CoV-2感染和疫苗接种后主要的泛冠状病毒特异性细胞和体液表位iCope的影响。在老年个体中，iCope反应性CD4 T细胞反应在数量和质量上均有所降低，TCR库狭窄，疫苗接种无法增强这种反应，而新出现的刺突突变会使其进一步受损。相比之下，泛冠状病毒反应性体液免疫仅受突变影响，不受年龄影响。我们的结果揭示了老年人群中泛冠状病毒免疫这一二分层面存在明显缺陷，这对于长期抵御SARS-CoV-2变异株至关重要。
