Protection by universal influenza vaccine is mediated by memory CD4 T cells

Vaccine. 2018 Jul 5;36(29):4198-4206. doi: 10.1016/j.vaccine.2018.06.007. Epub 2018 Jun 7.

Abstract

There is a diverse array of influenza viruses which circulate between different species, reassort and drift over time. Current seasonal influenza vaccines are ineffective in controlling these viruses. We have developed a novel universal vaccine which elicits robust T cell responses and protection against diverse influenza viruses in mouse and human models. Vaccine mediated protection was dependent on influenza-specific CD4+ T cells, whereby depletion of CD4+ T cells at either vaccination or challenge time points significantly reduced survival in mice. Vaccine memory CD4+ T cells were needed for early antibody production and CD8+ T cell recall responses. Furthermore, influenza-specific CD4+ T cells from vaccination manifested primarily Tfh and Th1 profiles with anti-viral cytokine production. The vaccine boosted H5-specific T cells from human PBMCs, specifically CD4+ and CD8+ T effector memory type, ensuring the vaccine was truly universal for its future application. These findings have implications for the development and optimization of T cell activating vaccines for universal immunity against influenza.

Keywords: IL-15; Influenza virus; T cells; Universal vaccine; Vaccinia.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Immunologic Memory*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, SCID
  • Survival Analysis

Substances

  • Influenza Vaccines