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

Award Number: R42AI120269
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2015
PERIOD OF PERFORMANCE END DATE: 06/30/2021

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Restimulating memory T cell responses in elderly by a novel, live influenza vaccine - 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 (> 65 years 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 Phase I, we showed that M2SR virus results in robust restimulation of memory CD4 and CD8 T cells in older humans without causing pathological inflammation by engaging non-inflammasome dependent innate pathways. In this Phase II proposal, we will explore how M2SR stimulates antiviral immune responses in older subjects in the following aims: Aim 1. Examine dendritic cell survival and function in response to M2SR infection. Aim 2: Determine the molecular mechanism of interferon stimulated gene expression regulation in dendritic cells. Aim 3: Evaluate the early immune response in human subjects vaccinated with M2SR. 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2018	FLUGEN, INC.	597 SCIENCE DR STE 10	MADISON	WI	53711	DANE	USA	Allergy and Infectious Diseases Research	000	3	12/7/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	FLUGEN, INC.	597 SCIENCE DR STE 10	MADISON	WI	53711	DANE	USA	Allergy and Infectious Diseases Research	000	3	11/25/2019	NON-COMPETING CONTINUATION	$0
2020	2018	FLUGEN, INC.	597 SCIENCE DR STE 10	MADISON	WI	53711	DANE	USA	Allergy and Infectious Diseases Research	001	3	6/2/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $1,087,654 )
2018	2018	FLUGEN, INC.	545 SCIENCE DR	MADISON	WI	53711	DANE	USA	Allergy and Infectious Diseases Research	000	3	7/18/2018	NON-COMPETING CONTINUATION	$737,654
2018	2018	FLUGEN, INC.	545 SCIENCE DR	MADISON	WI	53711	DANE	USA	Allergy and Infectious Diseases Research	001	3	8/13/2018	NON-COMPETING CONTINUATION	$350,000
														Subtotal = $1,087,654

Issue Date FY: 2017 ( Subtotal = $746,327 )
2017	2017	FLUGEN, INC.	545 SCIENCE DR	MADISON	WI	53711	DANE	USA	Allergy and Infectious Diseases Research	000	2	6/24/2017	COMPETING CONTINUATION	$746,327
														Subtotal = $746,327

Grand Total All Awards = $1,833,981

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

Award Number: R42AI120269

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2015

PERIOD OF PERFORMANCE END DATE: 06/30/2021

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