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EFFECT OF HELMINTH INFECTION ON HIV-1 VACCINES

Award Number: R01AI078787
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: 02/15/2008
PERIOD OF PERFORMANCE END DATE: 01/31/2013

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EFFECT OF HELMINTH INFECTION ON HIV-1 VACCINES - DESCRIPTION (provided by applicant): The worldwide AIDS epidemic is most devastating in developing countries where more than 40 million people are infected. The development of an HIV-1 vaccine for populations in southern Africa and other developing countries is the highest priority. The majority of inhabitants in developing countries are also infected with parasitic helminthes which drive Th2-biasing and immune suppression. Helminth infection suppresses immune responses to Th1-type vaccines, and the expansion of viral antigen specific CD4+ and CD8+ T cell responses. Th1-type and cytotoxic CD8+ T cell responses are the goal of the majority of HIV-1 candidate vaccines in development or in clinical trials. Thus, how helminth infection will impact not only the induction of robust T cell responses to candidate HIV-1 vaccines but also the durability of these T cell responses is an important question. DNA/Adenoviral vector vaccines have shown great success in driving systemic and or mucosal vaccine-specific antibody, CD4+ and CD8+ T cell responses to HIV-1, as well as other pathogens. Thus the first goal of this application is to determine if DNA/Adenoviral vector HIV-1 vaccines will induce strong vaccine specific T cell responses following elimination of helminth parasites. To mimic the scenario in developing countries, we next ask if these vaccine specific T cell responses are maintained in mice that become re-infected with helminth parasites. In this same regard we will determine how re-infection during the vaccination regimen impacts the induction of vaccine specific T cell responses. We will also determine whether F4/80+,Gr1+ suppressor macrophages and/or CD4+,CD25+ T regulatory cells play prominent roles in suppression of HIV-1 vaccine specific T cell responses in helminth mice. Lastly, because the majority of HIV-1 transmission in developing countries is via mucosal sites, we ask if helminth infection differentially impacts systemic vs mucosal HIV-1 vaccine specific T cell responses in helminth infected mice. The specific aims of this proposal are: 1) Will eradication of schistosome infection and restoration of normal immune bias allow for successful vaccination with HIV-1 candidate vaccines in mice? 2) Will established immune responses to HIV-1 vaccines remain durable or be altered by subsequent infection with immunomodulatory helminthes? 3) Does helminth infection differentially impact systemic vs mucosal HIV-1 vaccine specific T cell 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: 2012 ( Subtotal = $363,862 )
2012	2012	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC	BUSINESS SERVICES BUILDING	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	6	1/30/2012	NON-COMPETING CONTINUATION	$363,862
														Subtotal = $363,862

Issue Date FY: 2011 ( Subtotal = $363,862 )
2011	2011	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC	BUSINESS SERVICES BUILDING	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	001	5	6/8/2011	NON-COMPETING CONTINUATION	$33,078
2011	2011	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC	BUSINESS SERVICES BUILDING	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	5	1/20/2011	NON-COMPETING CONTINUATION	$330,784
														Subtotal = $363,862

Issue Date FY: 2010 ( Subtotal = $367,538 )
2010	2010	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC	BUSINESS SERVICES BUILDING	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	4	1/13/2010	NON-COMPETING CONTINUATION	$367,538
														Subtotal = $367,538

Issue Date FY: 2009 ( Subtotal = $382,929 )
2009	2009	HARVARD UNIVERSITY, SCHOOL OF PUBLIC HEALTH	55 SHATTUCK STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	2	9/28/2009	NON-COMPETING CONTINUATION	-$284,398
2009	2009	HARVARD UNIVERSITY, SCHOOL OF PUBLIC HEALTH	55 SHATTUCK STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	1/22/2009	NON-COMPETING CONTINUATION	$367,407
2009	2009	HARVARD UNIVERSITY, SCHOOL OF PUBLIC HEALTH	55 SHATTUCK STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	2	7/13/2009	NON-COMPETING CONTINUATION	$40,822
2009	2009	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC	BUSINESS SERVICES BUILDING	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	003	3	9/28/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$259,098
														Subtotal = $382,929

Issue Date FY: 2008 ( Subtotal = $407,500 )
2008	2008	HARVARD UNIVERSITY PRESIDENT & FELLOWS	HOLYOKE 466, 1350 MASS AVENUE	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	1	2/8/2008	NEW	$407,500
														Subtotal = $407,500

Grand Total All Awards = $1,885,691

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EFFECT OF HELMINTH INFECTION ON HIV-1 VACCINES

Award Number: R01AI078787

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: 02/15/2008

PERIOD OF PERFORMANCE END DATE: 01/31/2013

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