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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.

Original publication

DOI

10.1016/j.vaccine.2018.06.007

Type

Journal article

Journal

Vaccine

Publication Date

05/07/2018

Volume

36

Pages

4198 - 4206

Keywords

IL-15, Influenza virus, T cells, Universal vaccine, Vaccinia, Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Female, Immunologic Memory, Influenza Vaccines, Mice, Inbred BALB C, Mice, Nude, Mice, SCID, Survival Analysis