Effect of influenza A(H5N1) vaccine prepandemic priming on CD4+ T-cell responses

J Infect Dis. 2015 May 1;211(9):1408-17. doi: 10.1093/infdis/jiu616. Epub 2014 Nov 6.


Introduction: Previous priming with avian influenza vaccines results in more rapid and more robust neutralizing antibody responses upon revaccination, but the role CD4(+) T cells play in this process is not currently known.

Methods: Human subjects previously enrolled in trials of inactivated influenza A(H5N1) vaccines and naive subjects were immunized with an inactivated subunit influenza A/Indonesia/5/05(H5N1) vaccine. Neutralizing antibody responses were measured by a microneutralization assay, and hemagglutinin (HA)-specific and nucleoprotein (NP)-specific CD4(+) T-cell responses were quantified using interferon γ enzyme-linked immunosorbent spot assays.

Results: While vaccination induced barely detectable CD4(+) T-cell responses specific for HA in the previously unprimed group, primed subjects had readily detectable HA-specific memory CD4(+) T cells at baseline and mounted a more robust response to HA-specific epitopes after vaccination. There were no differences between groups when conserved NP-specific CD4(+) T-cell responses were examined. Interestingly, neutralizing antibody responses following revaccination were significantly higher in individuals who mounted a CD4(+) T-cell response to the H5 HA protein, a correlation not observed for NP-specific responses.

Conclusions: These findings suggest that prepandemic vaccination results in an enriched population of HA-specific CD4(+) T cells that are recruited on rechallenge with a drifted vaccine variant and contribute to more robust and more rapid neutralizing antibody responses.

Keywords: CD4+ T cells; H5N1; avian influenza; influenza; influenza vaccine; pandemic influenza.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4-Positive T-Lymphocytes / physiology*
  • Female
  • Humans
  • Immunization Schedule
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Pandemics / prevention & control


  • Influenza Vaccines