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Myeloid-derived Suppressor cells (MDSC) suppress infant immune responses

Award Number: R01AI100018
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: 04/01/2012
PERIOD OF PERFORMANCE END DATE: 03/31/2016

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Myeloid-derived Suppressor cells (MDSC) suppress infant immune responses - DESCRIPTION (provided by applicant): Almost 4 million infants under 6 months old die each year of infections, many of which are vaccine-preventable. The infant immune system cannot control infection, or respond to vaccination, as effectively as older children's or adults', which has been attributed to immunologic immaturity. Here, we have identified a mechanism to explain this reduced immunity in young infants: they possess innate regulatory cells, called myeloid-derived suppressor cells (MDSC), which are potent inhibitors of both NK cell and T cell activation. MDSC have never been described before in infants, and are rarely seen in healthy adults. MDSC have best been characterized in adult cancer patients where they have remarkable, albeit reversible, suppressive effects on anti-tumor T cell activity. Our overall hypothesis is that MDSC populations present in neonates and infants suppress infant NK and T cell responses resulting in inefficient responses to both infection and vaccination early in life. The aims addressed in this application will phenotypically and functionally define MDSC in cord blood. We will perform longitudinal studies in infants during the first year of life to assess the influence of MDSC on infant immune responses to routine childhood vaccines and infections. In addition, the aims will determine if suppression of neonatal NK and T cells by MDSC is arginase-1-dependent with the use of arginase-1 inhibitors. Finally we will determine if inhibition of MDSC function will abrogate their suppressive actions and enhance neonatal NK and T cell activity. The challenge of early life vaccination lies in the limitations of the infant immune response. Thus, it is pertinent to elucidate the mechanisms behind reduced neonatal immunity to illuminate ways to enhance infant immune responses.


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: 2021 ( Subtotal = -$61,354 )
2021	2015	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	002	4	10/3/2020	NON-COMPETING CONTINUATION	$61,354
2021	2015	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	10/1/2020	NON-COMPETING CONTINUATION	-$61,354
2021	2015	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	4	10/3/2020	NON-COMPETING CONTINUATION	-$61,354
														Subtotal = -$61,354

Issue Date FY: 2018 ( Subtotal = -$5,714 )
2018	2016	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	5	5/10/2018	EXTENSION WITH OR WITHOUT FUNDS	-$5,714
														Subtotal = -$5,714

Issue Date FY: 2017 ( Subtotal = $198,285 )
2017	2016	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	004	5	1/30/2017	EXTENSION WITH OR WITHOUT FUNDS	$66,095
2017	2016	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	5	1/25/2017	EXTENSION WITH OR WITHOUT FUNDS	-$66,095
2017	2016	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	006	5	1/30/2017	EXTENSION WITH OR WITHOUT FUNDS	-$66,095
2017	2016	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	005	5	1/30/2017	EXTENSION WITH OR WITHOUT FUNDS	$66,095
2017	2015	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	002	4	1/30/2017	NON-COMPETING CONTINUATION	$66,095
2017	2015	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	003	4	1/30/2017	NON-COMPETING CONTINUATION	$66,095
2017	2015	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	1/25/2017	NON-COMPETING CONTINUATION	$66,095
														Subtotal = $198,285

Issue Date FY: 2016 ( Subtotal = $340,032 )
2016	2016	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	5	3/17/2016	EXTENSION WITH OR WITHOUT FUNDS	$340,032
														Subtotal = $340,032

Issue Date FY: 2015 ( Subtotal = $552,710 )
2015	2015	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	3/17/2015	NON-COMPETING CONTINUATION	$342,934
2015	2015	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	4	8/24/2015	NON-COMPETING CONTINUATION	$209,776
														Subtotal = $552,710

Issue Date FY: 2014 ( Subtotal = $394,960 )
2014	2014	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	3	4/1/2014	NON-COMPETING CONTINUATION	$394,960
														Subtotal = $394,960

Issue Date FY: 2013 ( Subtotal = $408,528 )
2013	2013	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	2	3/22/2013	NON-COMPETING CONTINUATION	$375,180
2013	2013	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	2	5/31/2013	NON-COMPETING CONTINUATION	$33,348
														Subtotal = $408,528

Issue Date FY: 2012 ( Subtotal = $474,848 )
2012	2012	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	3/19/2012	NEW	$474,848
														Subtotal = $474,848

Grand Total All Awards = $2,302,295

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Myeloid-derived Suppressor cells (MDSC) suppress infant immune responses

Award Number: R01AI100018

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: 04/01/2012

PERIOD OF PERFORMANCE END DATE: 03/31/2016

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