Pre-existing immunity and vaccine history determine hemagglutinin-specific CD4 T cell and IgG response following seasonal influenza vaccination

Nat Commun. 2021 Nov 18;12(1):6720. doi: 10.1038/s41467-021-27064-3.


Effectiveness of seasonal influenza vaccination varies between individuals and might be affected by vaccination history among other factors. Here we show, by monitoring frequencies of CD4 T cells specific to the conserved hemagglutinin epitope HA118-132 and titres of IgG against the corresponding recombinant hemagglutinin protein, that antigen-specific CD4 T cell and antibody responses are closely linked to pre-existing immunity and vaccine history. Upon immunization, a strong early reaction is observed in all vaccine naïve participants and also in vaccine experienced individuals who have not received the respective seasonal vaccine in the previous year. This response is characterized by HA118-132 specific CD4 T cells with a follicular helper T cell phenotype and by ascending titers of hemagglutinin-specific antibodies from baseline to day 28 following vaccination. This trend was observed in only a proportion of those participants who received the seasonal vaccine the year preceding the study. Regardless of history, levels of pre-existing antibodies and CD127 expression on CD4 T cells at baseline were the strongest predictors of robust early response. Thus, both pre-existing immunity and vaccine history contribute to the response to seasonal influenza vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / immunology
  • ADP-ribosyl Cyclase 1 / metabolism
  • Adult
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Female
  • Hemagglutinins / chemistry
  • Hemagglutinins / immunology*
  • Humans
  • Immunoglobulin G / immunology*
  • Inducible T-Cell Co-Stimulator Protein / immunology
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / physiology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control
  • Influenza, Human / virology
  • Lymphocyte Activation / immunology
  • Male
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Seasons
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Vaccination / methods
  • Young Adult


  • Antibodies, Viral
  • Hemagglutinins
  • ICOS protein, human
  • Immunoglobulin G
  • Inducible T-Cell Co-Stimulator Protein
  • Influenza Vaccines
  • Membrane Glycoproteins
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1