The Negative Effect of Preexisting Immunity on Influenza Vaccine Responses Transcends the Impact of Vaccine Formulation Type and Vaccination History

J Infect Dis. 2023 Feb 1;227(3):381-390. doi: 10.1093/infdis/jiac068.

Abstract

The most effective measure to induce protection from influenza is vaccination. Thus, yearly vaccination is recommended, which, together with infections, establishes diverse repertoires of B cells, antibodies, and T cells. We examined the impact of this accumulated immunity on human responses in adults to split, subunit, and recombinant protein-based influenza vaccines. Enzyme-linked immunosorbent assay (ELISA) assays, to quantify serum antibodies, and peptide-stimulated CD4 T-cell cytokine ELISpots revealed that preexisting levels of hemagglutinin (HA)-specific antibodies were negatively associated with gains in antibody postvaccination, while preexisting levels of CD4 T cells were negatively correlated with vaccine-induced expansion of CD4 T cells. These patterns were seen independently of the vaccine formulation administered and the subjects' influenza vaccine history. Thus, although memory CD4 T cells and serum antibodies consist of components that can enhance vaccine responses, on balance, the accumulated immunity specific for influenza A H1 and H3 proteins is associated with diminished future responses.

Keywords: CD4 T cells; human immunity; immune memory; influenza; vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies
  • Antibodies, Viral
  • CD4-Positive T-Lymphocytes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Humans
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • Vaccination

Substances

  • Influenza Vaccines
  • Antibodies
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus