Coronavirus disease 2019(COVID-19)messenger RNA(mRNA)vaccines have succeeded unprecedentedly due to high protection efficacy and robust immune responses.However,systematic and longitudinal profiling of immune response...Coronavirus disease 2019(COVID-19)messenger RNA(mRNA)vaccines have succeeded unprecedentedly due to high protection efficacy and robust immune responses.However,systematic and longitudinal profiling of immune responses in mRNA vaccine recipients remains limited.Here,a cohort of ten healthy volunteers who received two doses of ARCoV,a non-modified mRNA vaccine,were enrolled.Peripheral blood samples were collected and analyzed using Olink technology,antibody detection,intracellular cytokine staining,single-cell sequencing,and T cell receptor(TCR)sequencing.ARCoV vaccination induced potent humoral and cellular immune responses,as well as elevated cytokines including CX-C motif chemokine ligand 10(CXCL10)and interferon-gamma(IFN-g).Single-cell sequencing revealed that ARCoV immunization induced an increased relative abundance of interferon-activated T cells,proliferative T cells,and naïve T cells.Monocytes and dendritic cells exhibited activation of the innate immune response,downregulation of hypoxia and glycolysis pathways,and a transient decrease in their proportions.Integrative analysis of single-cell RNA and TCR sequencing identified clonal expansion of effector T cells and killer cell immunoglobulin-like receptor(KIR)-expressing natural killer-like cells after the second dose.These findings deepen our understanding of the immune dynamics following mRNA vaccination and offer valuable insights for designing next-generation vaccines.This study was registered at the Chinese Clinical Trial Registry(ChiCTR2100049104).展开更多
基金supported by the National Key Research and Development Project of China(grant number 2021YFC2302400 to C.F.Q.)the National Natural Science Foundation of China(grant numbers 32130005 to C.F.Q.,92169120 to H.Z.,and 82172244 to X.W.).
文摘Coronavirus disease 2019(COVID-19)messenger RNA(mRNA)vaccines have succeeded unprecedentedly due to high protection efficacy and robust immune responses.However,systematic and longitudinal profiling of immune responses in mRNA vaccine recipients remains limited.Here,a cohort of ten healthy volunteers who received two doses of ARCoV,a non-modified mRNA vaccine,were enrolled.Peripheral blood samples were collected and analyzed using Olink technology,antibody detection,intracellular cytokine staining,single-cell sequencing,and T cell receptor(TCR)sequencing.ARCoV vaccination induced potent humoral and cellular immune responses,as well as elevated cytokines including CX-C motif chemokine ligand 10(CXCL10)and interferon-gamma(IFN-g).Single-cell sequencing revealed that ARCoV immunization induced an increased relative abundance of interferon-activated T cells,proliferative T cells,and naïve T cells.Monocytes and dendritic cells exhibited activation of the innate immune response,downregulation of hypoxia and glycolysis pathways,and a transient decrease in their proportions.Integrative analysis of single-cell RNA and TCR sequencing identified clonal expansion of effector T cells and killer cell immunoglobulin-like receptor(KIR)-expressing natural killer-like cells after the second dose.These findings deepen our understanding of the immune dynamics following mRNA vaccination and offer valuable insights for designing next-generation vaccines.This study was registered at the Chinese Clinical Trial Registry(ChiCTR2100049104).
