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Mol Ther . Essential Role of CD56dimNKG2C+ NK Cells Trained by SARS-CoV-2 Vaccines in Protecting Against COVID-19

tetano

Editor, Senior Moderator
Mol Ther


. 2025 May 30:S1525-0016(25)00401-0.
doi: 10.1016/j.ymthe.2025.05.031. Online ahead of print. Essential Role of CD56[SUP]dim[/SUP]NKG2C[SUP]+[/SUP] NK Cells Trained by SARS-CoV-2 Vaccines in Protecting Against COVID-19

Huiwen Zheng[SUP] 1 [/SUP], Yanli Chen[SUP] 2 [/SUP], Jing Li[SUP] 3 [/SUP], Yifan Zhang[SUP] 3 [/SUP], Heng Li[SUP] 1 [/SUP], Xin Zhao[SUP] 1 [/SUP], Zhanlong He[SUP] 3 [/SUP], Yun Liao[SUP] 3 [/SUP], Zihan Zhang[SUP] 3 [/SUP], Haijing Shi[SUP] 1 [/SUP], Fengmei Yang[SUP] 3 [/SUP], Yunguang Hu[SUP] 3 [/SUP], Yadong Li[SUP] 3 [/SUP], Jiali Li[SUP] 3 [/SUP], Yuping Zhao[SUP] 3 [/SUP], Xinglong Zhang[SUP] 3 [/SUP], Jingsi Yang[SUP] 4 [/SUP], Qihan Li[SUP] 5 [/SUP], Longding Liu[SUP] 6 [/SUP]



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Free article Abstract

The adaptive immune protection elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been proven to control the severity of novel coronavirus disease 2019 (COVID-19). However, the contributions of innate lymphoid cells formed from immunization are poorly defined in vaccine evaluation. Here, we highlight how the natural-killer (NK) and macrophage (Mϕ) cells' response, primed by the inactivated COVID-19 vaccine, is crucial to preventing lung injury. We propose that a specific subset of NK cells, marked CD56[SUP]dim[/SUP]CD16[SUP]+[/SUP]NKG2C[SUP]+[/SUP], along with M2-like Mϕ, CD8[SUP]+[/SUP] T cells, are important in defending against SARS-CoV-2. Our studies using a rhesus-macaque (RM) model showed that this orchestration of protection was depicted as a trajectory of adaptive NK and Mϕ cell responses from circulating peripheral blood mononuclear cells (PBMCs) to the lungs. Through single-cell RNA sequencing (scRNA-seq) and mass cytometry (cytometry by time-of-flight, CyTOF) analysis, we also identified the significance of adaptive CD56[SUP]dim[/SUP]CD16[SUP]+[/SUP]CD57[SUP]+[/SUP]NKG2C[SUP]+[/SUP] NK cells and classical monocytes (CMs) with chemotaxis traits in orchestrating T-cell immunity in humans. Interestingly, our findings show a deficiency of these adaptive cells in older participants post-booster vaccination, leading to potentially inadequate protection. This study discusses the evaluation of vaccines at the innate immune level, which can contribute to the development of successful vaccines.


 
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