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Boosting anti-HIV immunity through manipulation of Tfh function.

Award Number: R01AI106482
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: 06/01/2013
PERIOD OF PERFORMANCE END DATE: 05/31/2018

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Boosting anti-HIV immunity through manipulation of Tfh function. - DESCRIPTION (provided by applicant): Viral suppression in the majority of HIV infected subjects can only be achieved with ART. Despite the significant decrease in inflammation and immune activation following ART, people under ART still exhibit low levels of both these activities leading to significant immune dysfunction that is illustrated by the inability to generae and maintain T cell and B cell immunity. Furthermore, ART therapy induces long and short-term toxicities leading to cardiovascular diseases and other complications. We have recently reported a significant dysfunction in the memory CD4 compartment in virally suppressed individuals undergoing ART. We have also shown a similar defect in the memory B cell compartment with these cells dying prematurely and producing significantly lower levels of anti-HIV antibodies when compared to natural controllers. Even when treated in the first few weeks after infection, only a small percentage of HIV infected subjects are able to contain viremia upon cessation of ART. Whereas, the large majority of HIV infected individuals exhibit resurgence of viremia demonstrating the inability of the immune system to contain viral replication in the absence of ART. This provides a strong rationale to develop novel immunotherapies that aim at augmenting anti-HIV immunity in chronically infected individuals in the absence of ART with the purpose of achieving a functional cure. Thus the inability to achieve a functional immune response against HIV upon treatment interruption in virally suppressed subjects is a major problem. Thus, for the majority of HIV infected individuals (more than 85%), the goal of acquiring anti-HIV immunity in the absence of ART is only possible with the augmentation of adaptive immune responses. In this proposal we will study the underlying mechanisms that could be responsible for their defective immune response in an effort of moving closer towards achieving a functional cure. We will further work under the educated assumption that enhancing the CD4+Tfh/B cell axis is critical for attaining improved anti-HIV immunity.


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 = $0 )
2020	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	5	11/7/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $546,312 )
2017	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	5	5/22/2017	NON-COMPETING CONTINUATION	$546,312
														Subtotal = $546,312

Issue Date FY: 2016 ( Subtotal = $551,007 )
2016	2016	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	4	5/12/2016	NON-COMPETING CONTINUATION	$551,007
														Subtotal = $551,007

Issue Date FY: 2015 ( Subtotal = $551,007 )
2015	2015	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	3	6/30/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$551,007
														Subtotal = $551,007

Issue Date FY: 2014 ( Subtotal = $659,763 )
2014	2014	VACCINE & GENE THERAPY INSTITUTE-FLORIDA	9801 SOUTHWEST DISCOVERY WAY	PORT SAINT LUCIE	FL	34987	SAINT LUCIE	USA	Allergy and Infectious Diseases Research	000	2	5/13/2014	NON-COMPETING CONTINUATION	$659,763
														Subtotal = $659,763

Issue Date FY: 2013 ( Subtotal = $524,241 )
2013	2013	VACCINE GENE THERAPY INSTITUTE-FLORIDA	11350 SW VILLAGE PARKWAY	PORT SAINT LUCIE	FL	34987	SAINT LUCIE	USA	Allergy and Infectious Diseases Research	000	1	5/23/2013	NEW	$524,241
														Subtotal = $524,241

Grand Total All Awards = $2,832,330

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Boosting anti-HIV immunity through manipulation of Tfh function.

Award Number: R01AI106482

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: 06/01/2013

PERIOD OF PERFORMANCE END DATE: 05/31/2018

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