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Optimizing HIV immunogen-BCR interactions for vaccine development

Award Number: P01AI094419
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: 05/01/2011
PERIOD OF PERFORMANCE END DATE: 09/30/2014

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Optimizing HIV immunogen-BCR interactions for vaccine development - DESCRIPTION (provided by applicant): The elicitation of potent and broad anti-HIV-1 neutralizing antibodies (NAbs) by immunization has been one of the major goals of HIV research since the beginning of the HIV/AIDS epidemic. So far, this goal has not been attained. The target of anti-HIV-1 NAbs is the viral envelope glycoprotein (Env) and several forms of HIV Env have been tested as immunogens over the past three decades. The lack of elicitation of antibodies with broad neutralizing activities by soluble Env immunogens is not due to the absence of relevant epitopes on such constructs. Understanding why conserved neutralization epitopes are poorly immunogenic during immunization by HIV Env constructs is the focus of this proposal. Our overall hypothesis is that the biophysical characteristics of the epitope-BCR interaction, especially the kon and koff binding rates of that interaction, dictate the downstream intracellular events that lead to either B cell-differentiation and antibody production, or to B cell-anergy. To test this hypothesis we propose a series of iterative studies that will improve our understanding of the structural and biophysical characteristics of immunogen-BCR interactions and of how these interactions influence downstream events that lead to B cell activation or anergy. Our team is composed of groups with diverse expertise that have a documented record of collaboration. Dr. Schief's group at the University of Washington is leading our immunogen-design efforts. Dr. Strong's group at the Fred Hutchinson Cancer Research Center is leading our efforts to characterize the structure of immunogens and the antibodies they elicit and their biophysical interactions. Dr. Stamatatos' group is leading our efforts to analyze the interaction of our immunogens with B cells. We are supported in our efforts by Dr. Atchison's group at the Institute for Systems Biology who will define those intracellular events that lead to optimal B cell stimulation and those that lead to B cell anergy or apoptosis, following the binding of b12 scaffolds on the BCR on B cells.


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: 2020 ( Subtotal = -$13,769 )
2020	2014	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	4	10/1/2019	NON-COMPETING CONTINUATION	-$9,866
2020	2014	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	10/1/2019	NON-COMPETING CONTINUATION	-$3,903
														Subtotal = -$13,769

Issue Date FY: 2018 ( Subtotal = -$924 )
2018	2015	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	6	8/28/2018	NON-COMPETING CONTINUATION	-$924
														Subtotal = -$924

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2015	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	6	4/20/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2014	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	1/20/2016	NON-COMPETING CONTINUATION	$13,769
2016	2014	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	5	1/21/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$13,769
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $2,200,648 )
2015	2015	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	002	6	5/4/2015	NON-COMPETING CONTINUATION	$2,046,594
2015	2014	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	5	1/19/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,958,486
2015	2014	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	1/16/2015	NON-COMPETING CONTINUATION	-$1,804,432
														Subtotal = $2,200,648

Issue Date FY: 2014 ( Subtotal = $2,175,195 )
2014	2014	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	4	8/8/2014	NON-COMPETING CONTINUATION	$108,993
2014	2014	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	4/23/2014	NON-COMPETING CONTINUATION	$2,066,202
														Subtotal = $2,175,195

Issue Date FY: 2013 ( Subtotal = $2,124,372 )
2013	2013	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	3	5/15/2013	NON-COMPETING CONTINUATION	$2,124,372
														Subtotal = $2,124,372

Issue Date FY: 2012 ( Subtotal = $2,180,408 )
2012	2012	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	2	4/26/2012	NON-COMPETING CONTINUATION	$2,180,408
														Subtotal = $2,180,408

Issue Date FY: 2011 ( Subtotal = $1,935,501 )
2011	2011	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	4/26/2011	NEW	$1,935,501
														Subtotal = $1,935,501

Grand Total All Awards = $10,601,431

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Optimizing HIV immunogen-BCR interactions for vaccine development

Award Number: P01AI094419

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: 05/01/2011

PERIOD OF PERFORMANCE END DATE: 09/30/2014

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