Restimulating memory T cell responses in elderly by a novel, live influenza vaccine

DESCRIPTION provided by applicant Respiratory infections with influenza viruses cause severe morbidity and mortality in humans and animals worldwide Importantly in humans the majority of morbidity and mortality following flu infection is seen in older individuals andgt year old Yet clear understanding of how aging impacts on innate immune responses and how to improve vaccine design in this age group is lacking Restimulating preexisting memory T cells against conserved epitopes in influenza virus by a vaccine might confer protective immunity in this age group An ideal vaccine for elderly should therefore engage pattern recognition receptors PRRs that activate antigen presenting cells APCs generate conserved antigenic epitopes while avoiding overt inflammatory responses In this proposal we will test the hypothesis that engaging non inflammasome dependent innate pathways by M SR virus results in robust restimulation of memory CD and CD T cells in older humans without causing pathological inflammation Aim To examine the transcriptome signature following infection with M SR vaccine in dendritic cells from old vs young adults Aim To examine ex vivo efficacy of M SR in restimulating functional anti influenza CD and CD memory T cells in the elderly Aim To determine the adjuvants that enhance the capacity of M SR to restimulate flu specific memory T cells in APCs from older adults These experiments are aimed at improving protection of older humans from influenza mediated disease by understanding the fundamental innate immune defects that contribute to failure to mount protective immunity The outcome of the experiments is expected to have high impact both with respect to the fundamental understanding of the underlying mechanism of flu related illnesses in the susceptible elderly population and in providing a basis with which to design vaccine and immunotherapeutic interventions PUBLIC HEALTH RELEVANCE Respiratory infections with influenza viruses cause severe morbidity and mortality in humans and animals worldwide Importantly in humans the majority of morbidity and mortality following flu infection is seen in older individuals andgt years old Yt clear understanding of how aging impacts on innate immune responses and how to improve vaccine design in this age group is lacking In this proposal we will test the hypothesis that engaging non inflammasome dependent innate pathways by M SR virus results in robust restimulation of memory CD and CD T cells in older humans without causing pathological inflammation