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The effect of peptide therapy and allergen provocation on Fel d1-specific T Cells

Award Number: U19AI100266
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/09/2012
PERIOD OF PERFORMANCE END DATE: 03/31/2019

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The effect of peptide therapy and allergen provocation on Fel d1-specific T Cells - The proposed Allergen Epitope Research and Validation Center will use unique Major Histocompatibility (MHO) class II tetramers containing T cell epitopes of the major cat allergen Pel d 1 in order to characterize allergen-specific T cells before and after intervention with (1) a peptide-based therapeutic vaccine comprised of immunodominant T cell epitopes of Pel d 1, and (2) bronchial (segmental) allergen challenge with cat allergen extract. Two research Projects and two Cores are proposed. The Cores (Administrative Core A and Clinical Trial Core B) will facilitate and support the scientific objectives and goals of the research Projects. Project 1 (peptide immunotherapy) Specific Aim 1 will use tetramers to both enrich and identify allergenspecific T cells in frozen peripheral blood mononuclear cell (PBMC) samples (before vs. after treatment) from a completed clinical trial of the peptide vaccine. Project 1 Specific Aim 2 will employ a prospective clinical trial of peptide immunotherapy to generate larger blood samples for more in depth analysis of the frequency and functional phenotype of allergen-specific (tetramer+) T cells. Project 1 Specific Aim 3 will address the relationship between peptide affinity for MHC molecules and efficacy. This Aim will be performed in HLA-DR transgenic mice as the research question posed cannot be answered in human subjects. Project 2 (bronchial allergen challenge) Specific Aims 1 & 2 will involve segmental allergen challenge in 48 catallergic asthmatic subjects. Samples of blood and bone marrow will be taken before and 24 hours after allergen challenge. Samples of bronchoalveolar lavage (BAL) fluid will be recovered from saline and allergen challenged lung lobes 24 hours after challenge. In all samples. Pel d 1 tetramers will be used to enrich (were appropriate) and identify allergen-specific T cells for further analysis of frequency and functional phenotype in each anatomical compartment. Project 2 Specific Aim 3 will perform a similar analysis but in HLA-DR4 transgenic mice, but will analyze several other compartments not accessible in human subjects (spleen, lung tissue, draining lymph nodes in addition to blood, BAL and bone marrow). Additionally this Aim will assess the effects of peptide immunotherapy in the murine allergen challenge model


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: 2019 ( Subtotal = -$216,214 )
2019	2018	MCMASTER UNIVERSITY	1280 MAIN ST W SUITE 20	HAMILTON	ON	L8S 4L8		CAN	Allergy and Infectious Diseases Research	001	5	9/4/2019	SUPPLEMENT FOR EXPANSION	-$161,981
2019	2016	MCMASTER UNIVERSITY	1280 MAIN ST W SUITE 20	HAMILTON	ON	L8S 4L8		CAN	Allergy and Infectious Diseases Research	000	5	9/4/2019	NON-COMPETING CONTINUATION	-$54,233
														Subtotal = -$216,214

Issue Date FY: 2018 ( Subtotal = $161,981 )
2018	2018	MCMASTER UNIVERSITY	1280 MAIN ST W SUITE 20	HAMILTON	ON	L8S 4L8		CAN	Allergy and Infectious Diseases Research	001	5	8/3/2018	SUPPLEMENT FOR EXPANSION	$161,981
2018	2016	MCMASTER UNIVERSITY	1280 MAIN ST W SUITE 20	HAMILTON	ON	L8S 4L8		CAN	Allergy and Infectious Diseases Research	000	5	8/1/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $161,981

Issue Date FY: 2016 ( Subtotal = $1,236,590 )
2016	2016	MCMASTER UNIVERSITY	1200 MAIN STREET WEST	HAMILTON				CAN	Allergy and Infectious Diseases Research	000	5	3/31/2016	NON-COMPETING CONTINUATION	$1,236,590
														Subtotal = $1,236,590

Issue Date FY: 2015 ( Subtotal = $1,239,733 )
2015	2015	MCMASTER UNIVERSITY	1200 MAIN STREET WEST	HAMILTON				CAN	Allergy and Infectious Diseases Research	000	4	3/19/2015	NON-COMPETING CONTINUATION	$1,239,733
														Subtotal = $1,239,733

Issue Date FY: 2014 ( Subtotal = $1,292,577 )
2014	2014	MCMASTER UNIVERSITY	1200 MAIN STREET WEST	HAMILTON				CAN	Allergy and Infectious Diseases Research	000	3	3/14/2014	NON-COMPETING CONTINUATION	$1,292,577
														Subtotal = $1,292,577

Issue Date FY: 2013 ( Subtotal = $1,248,202 )
2013	2013	MCMASTER UNIVERSITY	1200 MAIN ST. WESTHSC 1B7	HAMILTON				CAN	Allergy and Infectious Diseases Research	002	2	6/24/2013	EXTENSION WITH OR WITHOUT FUNDS	$14,501
2013	2013	MCMASTER UNIVERSITY	1200 MAIN ST. WESTHSC 1B7	HAMILTON				CAN	Allergy and Infectious Diseases Research	001	2	6/13/2013	EXTENSION WITH OR WITHOUT FUNDS	$38,611
2013	2013	MCMASTER UNIVERSITY	1200 MAIN ST. WESTHSC 1B7	HAMILTON				CAN	Allergy and Infectious Diseases Research	000	2	4/12/2013	EXTENSION WITH OR WITHOUT FUNDS	$1,195,090
														Subtotal = $1,248,202

Issue Date FY: 2012 ( Subtotal = $1,330,917 )
2012	2012	MCMASTER UNIVERSITY	1200 MAIN STREET WEST	HAMILTON, ONTARIO				CAN	Allergy and Infectious Diseases Research	000	1	4/6/2012	NEW	$1,330,917
														Subtotal = $1,330,917

Grand Total All Awards = $6,293,786

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The effect of peptide therapy and allergen provocation on Fel d1-specific T Cells

Award Number: U19AI100266

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 04/09/2012

PERIOD OF PERFORMANCE END DATE: 03/31/2019

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