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Hum Vaccin Immunother . Single-cell analysis unravels the role of NK cells and monocytes in the control of SARS-CoV-2 breakthrough infections in va

tetano

Editor, Senior Moderator
Hum Vaccin Immunother


. 2025 Dec;21(1):2534219.
doi: 10.1080/21645515.2025.2534219. Epub 2025 Jul 29. Single-cell analysis unravels the role of NK cells and monocytes in the control of SARS-CoV-2 breakthrough infections in vaccinated individuals

Huiwen Zheng[SUP] 1 2 3 [/SUP], Jing Li[SUP] 1 [/SUP], Xin Zhang[SUP] 1 [/SUP], Yun Liao[SUP] 1 2 3 [/SUP], Heng Li[SUP] 1 2 3 [/SUP], Xin Zhao[SUP] 1 2 3 [/SUP], Zihan Zhang[SUP] 1 [/SUP], Jingjing Wang[SUP] 1 2 3 [/SUP], Li Yu[SUP] 1 2 3 [/SUP], Dandan Li[SUP] 1 2 3 [/SUP], Heng Zhao[SUP] 1 2 3 [/SUP], Haijing Shi[SUP] 1 2 3 [/SUP], Longding Liu[SUP] 1 2 3 [/SUP]



Affiliations
Abstract

Analyzing the antiviral response of natural killer (NK) cells and monocytes is essential to understanding vaccine protection in an immunized population facing SARS-CoV-2 variant breakthrough infections (BTIs). In this study, in peripheral blood mononuclear cells (PBMCs) from vaccinated individuals with SARS-CoV-2 infections, we observed an increase in adaptive CD57[SUP]+[/SUP]NKG2C[SUP]+[/SUP] NK cells and classical monocytes (CMs). Single-cell sequencing analysis showed that the transcriptomic profiles of IFN-induced IFIT3 and other IFN-stimulated genes exhibited marked upregulation in NK cells, defined as CD56[SUP]dim[/SUP]CD57[SUP]+[/SUP]NKG2C[SUP]+[/SUP]IFIT3[SUP]+[/SUP] NK cells. Additionally, CM in the blood showed characteristics indicative of differentiation into dendritic cells (DCs) and macrophages, which further evidenced their potential antiviral functions. Our study indicates that a vaccinated population rapidly activates an antiviral innate immune response following a BTI, thus revealing a link to the control of viral replication during SARS-CoV-2 BTIs.

Keywords: SARS-CoV-2 breakthrough infection; adaptive NK cells; antiviral innate immunity; classical monocytes; scRNA-seq.

 
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