Influenza vaccine induces intracellular immune memory of human NK cells

PLoS One. 2015 Mar 17;10(3):e0121258. doi: 10.1371/journal.pone.0121258. eCollection 2015.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Differentiation / immunology*
  • Female
  • Humans
  • Immunologic Memory / drug effects*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Interferon-gamma / immunology*
  • Killer Cells, Natural / immunology*
  • Male
  • Middle Aged

Substances

  • Antigens, Differentiation
  • IFNG protein, human
  • Influenza Vaccines
  • Interferon-gamma

Grants and funding

This work was supported by grants from the Natural Science Foundation of China (#81330071, #31021061) and the National Basic Research Project (973 Project 2012CB519004, 2013CB944902, 2013CB530506). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.