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IMMUNE RESPONSE TO P. VIVAX IN DUFFY (-) HUMANS

Award Number: R01AI057592
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: 08/09/2010
PERIOD OF PERFORMANCE END DATE: 07/31/2011

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IMMUNE RESPONSE TO P. VIVAX IN DUFFY (-) HUMANS - DESCRIPTION (provided by the applicant): At least 20% of the 300-500 million annual cases of malaria are caused by infection with Plasmodium vivax. Although P. vivax malaria is rarely lethal, it causes a great deal of human suffering and inhibits economic development in many malaria-endemic countries. P. vivax is relatively little studied compared to the most lethal human malaria parasite P. falciparum, primarily because it cannot be cultured in vitro. Consequently, far less progress has been achieved in P. vivax vaccine development compared to P. falciparum. Invasion of P. vivax merozoites into reticulocytes is dependent upon the expression of the Duffy antigen/receptor for chemokines (DARC) on the reticulocyte surface. Individuals lacking DARC [F(y-)J are completely resistant to infection by P. vivax blood stages, but should be susceptible to liver stage infections initiated by the invasion of sporozoites. Furthermore, liver stage parasites should develop normally in Fy(-) individuals, but the merozoites released from the liver would not be expected to initiate blood stage infections. Consequently, Fy(-) individuals residing in P. vivax endemic areas who are exposed to infected mosquitoes should exhibit immune responses primarily to liver stage antigens, whereas Fy(+) individuals should respond to both liver and blood stage antigens, with a predominant response directed to the blood stage antigens. It should be possible to use lymphocytes from Fy(-) individuals in novel assays proposed here to identify pre-erythrocytic stage P. vivax antigens that are targets of cellular immune responses. Lymphocytes and sera will be collected from Fy(+) and Fy(-) individuals living in P. vivax endemic areas in Columbia. Novel ELISPOT assays and IF As will be used to characterize the immune responses to 100 novel proteins identified from the P. vivax genome sequence. Immunogenicity studies will be conducted in mice to confirm that the antigenic proteins identified through the in vitro screening process in human immune cells are immunogenic in vivo, and to generate the antisera for subcellular localization to confirm the stage specificity of the novel antigens.


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: 2010 ( Subtotal = $338,901 )
2010	2010	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Trans-NIH Recovery Act Research Support	000	6	8/9/2010	SUPPLEMENT FOR EXPANSION	$338,901
														Subtotal = $338,901

Issue Date FY: 2009 ( Subtotal = $429,615 )
2009	2009	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	6	7/9/2009	NON-COMPETING CONTINUATION	$42,961
2009	2009	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	6	11/26/2008	NON-COMPETING CONTINUATION	$386,654
														Subtotal = $429,615

Issue Date FY: 2008 ( Subtotal = $425,871 )
2008	2008	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	5	1/3/2008	NON-COMPETING CONTINUATION	$425,871
														Subtotal = $425,871

Issue Date FY: 2007 ( Subtotal = $434,119 )
2007	2007	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	12/27/2006	NON-COMPETING CONTINUATION	$434,119
														Subtotal = $434,119

Issue Date FY: 2006 ( Subtotal = $427,890 )
2006	2006	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N, STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	3	7/18/2006	NON-COMPETING CONTINUATION	$427,890
														Subtotal = $427,890

Issue Date FY: 2005 ( Subtotal = $307,712 )
2005	2005	INSTITUTE FOR GENOMIC RESEARCH (THE)	9712 MEDICAL CENTER DRIVE	ROCKVILLE	MD	20850	MONTGOMERY	USA	Microbiology and Infectious Diseases Research	000	1	3/25/2005	NEW	$307,712
														Subtotal = $307,712

Grand Total All Awards = $2,364,108

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IMMUNE RESPONSE TO P. VIVAX IN DUFFY (-) HUMANS

Award Number: R01AI057592

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: 08/09/2010

PERIOD OF PERFORMANCE END DATE: 07/31/2011

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