title: Influenza vaccine induces intracellular immune memory of human NK cells.
abstract: Influenza vaccines elicit antigen-specific antibodies and immune memory to protect humans from infection with drift variants. However, what supports or limits vaccine efficacy and duration is unclear. Here, we vaccinated healthy volunteers with annual vaccine formulations and investigated the dynamics of T cell, natural killer (NK) cell and antibody responses upon restimulation with heterologous or homologous influenza virus strains. Influenza vaccines induced potential memory NK cells with increased antigen-specific recall IFN-γ responses during the first 6 months. In the absence of significant changes in other NK cell markers (CD45RO, NKp44, CXCR6, CD57, NKG2C, CCR7, CD62L and CD27), influenza vaccines induced memory NK cells with the distinct feature of intracellular NKp46 expression. Indeed, surface NKp46 was internalized, and the dynamic increase in NKp46(intracellular)+CD56dim NK cells positively correlated with increased IFN-γ production to influenza virus restimulation after vaccination. In addition, anti-NKp46 antibodies blocked IFN-γ responses. These findings provide insights into a novel mechanism underlying vaccine-induced immunity and NK-related diseases, which may help to design persisting and universal vaccines in the future.
authors.affiliation: Institute of Immunology, School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Institute of Immunology, School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Binqing
authors.initials: B
authors.lastname: Fu
authors.affiliation: Institute of Immunology, School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Institute of Immunology, School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Li
authors.affiliation: Anhui Provincial Center for Disease Control and Prevention, Hefei, China.
authors.forename: Wanfu
authors.initials: W
authors.lastname: Hu
authors.affiliation: Institute of Immunology, School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Institute of Immunology, School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D000328:Adult; D000943:Antigens, Differentiation / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D000943:Antigens, Differentiation; C573415:IFNG protein, human; D007252:Influenza Vaccines; D007371:Interferon-gamma