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Vaccine. 2018 Jun 7. pii: S0264-410X(18)30818-1. doi: 10.1016/j.vaccine.2018.06.007. [Epub ahead of print]
Protection by universal influenza vaccine is mediated by memory CD4 T cells.
Valkenburg SA1, Li OTW2, Li A1, Bull M1, Waldmann TA3, Perera LP3, Peiris M2, Poon LLM4.
Author information
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
PMID: 29887326 DOI: 10.1016/j.vaccine.2018.06.007
Protection by universal influenza vaccine is mediated by memory CD4 T cells.
Valkenburg SA1, Li OTW2, Li A1, Bull M1, Waldmann TA3, Perera LP3, Peiris M2, Poon LLM4.
Author information
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
PMID: 29887326 DOI: 10.1016/j.vaccine.2018.06.007