Research Topic

T-cell immunity to influenza

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Influenza continues to be a major global public health burden with significant annual morbidity and economic costs. This annual burden is allied to the constant overhanging sceptre of a severe pandemic. A major obstacle in combating influenza is viral evolution that leads to the continuous emergence of new ...

Influenza continues to be a major global public health burden with significant annual morbidity and economic costs. This annual burden is allied to the constant overhanging sceptre of a severe pandemic. A major obstacle in combating influenza is viral evolution that leads to the continuous emergence of new antigenically distinct virus strains to evade protective host immunity. Thus, there is great interest in understanding the immunological mechanisms involved in protection against a broad range of influenza virus subtypes. This understanding of heterosubtypic immunity is particularly important for the development and evaluation of “universal” influenza vaccines designed to confer broad protective immunity.

T-cells are a critical component in mediating heterosubtypic immunity, particularly in the absence of antibody mediated protection. T-cells, CD4+ and CD8+, have been shown to recognise epitopes in the internal viral proteins that are highly conserved across subtypes of influenza A virus and T-cells have been shown to mediate protection in multiple animal and non-human primate models of influenza. More recently, multiple strands of research has enhanced our understanding of cellular immunity to influenza. In particular, this includes work on the protective role of CD8+ T-cells in humans during a pandemic, the direct and indirect contribution of CD4+ T-cells, the protective role of local tissue-resident memory T-cells and the contribution of T follicular helper cells in B cell mediated protection against influenza. At the same time, there has been a greater understanding of the immune mechanisms involved in influenza immunopathology and the role of different T-cells in recovery and resolution of influenza. Furthermore, there has been increasing interest in the molecular mechanisms including transcriptional and epigenetic changes that underlie the induction and development of protective T-cell memory as well as defining the basis of T-cell specificity. In parallel, there has been rapid progress in developing and clinical evaluation of vaccines and vaccination strategies to induce cross-protective T-cells using live and vector-based vaccines.

In this Research Topic, we focus on charting the historical and recent paradigm shifting advances in our understanding of the fundamental biology of T-cell immunity to influenza as well as highlighting translational applications in developing protective cellular correlates and T-cell inducing influenza vaccines.


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