Abstract
Current flu vaccines rely on the induction of strain-specific neutralizing antibodies, which leaves the population vulnerable to drifted seasonal or newly emerged pandemic strains. Therefore, universal flu vaccine approaches that induce broad immunity against conserved parts of influenza have top priority in research. Cross-reactive T cell responses, especially tissue-resident memory T cells in the respiratory tract, provide efficient heterologous immunity, and must therefore be a key component of universal flu vaccines. Here, we review recent findings about T cell-based flu immunity, with an emphasis on tissue-resident memory T cells in the respiratory tract of humans and different animal models. Furthermore, we provide an update on preclinical and clinical studies evaluating T cell-evoking flu vaccines, and discuss the implementation of T cell immunity in real-life vaccine policies.
Highlights
Long Way from Animal ModelsInfluenza viruses are a constant threat to the world community
This review summarizes recent flu vaccine strategies and their shortcomings, the potential of cross-reactive T cell responses in flu immunity, and the remaining challenges for the clinical use of T cell-evoking influenza vaccines
While being a proof-of-principle for T cell-mediated heterologous immunity (Het-I), LAIVs do not present a vaccine option for all age groups, and they suffer from low vaccine efficacy (VE) in some seasons [29,30,31]
Summary
Influenza viruses are a constant threat to the world community. Globally, 290,000–. The error-prone viral polymerase of IAV and IBV lacks a proofreading activity, leading to a continuous accumulation of mutations, especially in the surface proteins hemagglutinin (HA) or neuraminidase (NA) [6,7], while the internal virus proteins remain more conserved. This phenomenon called “genetic drift” allows the genetic evolution of seasonal flu strains. “Genetic shift” occurs only in IAV, and describes the exchange of one or more gene segments among different IAV strains upon superinfection, leading to novel virus subtypes By this mechanism, novel viruses can emerge against which weak or no herd immunity exists in the human population [8]. This review summarizes recent flu vaccine strategies and their shortcomings, the potential of cross-reactive T cell responses in flu immunity, and the remaining challenges for the clinical use of T cell-evoking influenza vaccines
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