Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
JCI Insight. 2023 Nov 22;8(22):e172510. doi: 10.1172/jci.insight.172510.
Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine-induced memory T cells limit lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T cell responses and showed similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells. Both monovalent and bivalent mRNA vaccines elicited strong expansion of a heterogeneous pool of terminal effectors and memory precursor effector CD8 T cells in spleen, inguinal and mediastinal lymph nodes, pulmonary vasculature, and most surprisingly in the airways, suggestive of systemic and regional surveillance. Furthermore, we document that: (a) CD8 T cell memory persists in multiple tissues for > 200 days; (b) following challenge with pathogenic SARS-CoV-2, circulating memory CD8 T cells rapidly extravasate to the lungs and promote expeditious viral clearance, by mechanisms that require CD4 T cell help; and (c) adoptively transferred splenic memory CD8 T cells traffic to the airways and promote lung SARS-CoV-2 clearance. These findings provide insights into the critical role of memory T cells in preventing severe lung disease following breakthrough infections with antibody-evasive SARS-CoV-2 variants.
尽管 SARS-CoV-2 的进化产生了源源不断的逃避抗体的病毒变异株,但 COVID-19 mRNA 疫苗为预防严重疾病和住院提供了强大的保护。在这里,我们想知道 mRNA 疫苗诱导的记忆 T 细胞是否会限制肺部 SARS-CoV-2 的复制和严重疾病。我们发现,接受 BioNTech mRNA 疫苗加强针的小鼠和人类产生了强大的 CD8 T 细胞反应,并表现出相似的颗粒酶 B/穿孔素表达效应 CD8 T 细胞扩增和收缩的动力学。单价和双价 mRNA 疫苗在脾、腹股沟和纵隔淋巴结、肺血管以及最令人惊讶的是在气道中强烈扩增了一个异质的终末效应器和记忆前体效应 CD8 T 细胞池,提示存在全身和区域性监测。此外,我们还证明:(a)CD8 T 细胞记忆在多个组织中持续存在超过 200 天;(b)在受到致病性 SARS-CoV-2 挑战后,循环记忆 CD8 T 细胞迅速外渗到肺部,并通过需要 CD4 T 细胞辅助的机制促进病毒迅速清除;(c)脾记忆 CD8 T 细胞通过转移到气道并促进肺部 SARS-CoV-2 清除。这些发现为记忆 T 细胞在预防逃避抗体的 SARS-CoV-2 变异株突破性感染后发生严重肺部疾病方面的关键作用提供了见解。
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