Protection by universal influenza vaccine is mediated by memory CD4 T cells. Issue 29 (5th July 2018)

• Record Type: Journal Article
• Authors: Valkenburg, Sophie A.; Li, Olive T.W.; Li, Athena; Bull, Maireid; Waldmann, Thomas A.; Perera, Liyanage P.; Peiris, Malik; Poon, Leo L.M.
• Is Part Of: Vaccine. Volume 36:Issue 29(2018)
• Page Start: 4198
• Page End: 4206
• Publication Date: 2018-07-05
• Subjects: Influenza virus -- T cells -- Universal vaccine -- IL-15 -- Vaccinia; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.06.007
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: A vaccinia-based universal influenza vaccine was previously developed by us. Influenza virus-specific CD4 + T cells were found to be important for protection. Vaccine-induced memory CD4 + T cells were needed for early antibody production. Vaccine-induced memory CD4 + T cells were needed for early CD8 + recall responses. Human influenza-specific T cells could be recruited and expanded by the vaccine. 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.