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Multi-target blood stage vaccine against Plasmodium falciparum

Award Number: R01AI144014
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: 12/13/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Multi-target blood stage vaccine against Plasmodium falciparum - Project Summary The overall aim of this application is to advance PfCDPK5 and PfGARP as vaccine candidates for falciparum malaria. P.falciparum malaria affects almost one-half of the world's population and causes more than 500,000 deaths annually. Young children in malaria endemic areas of Africa have the highest mortality rate because of their immature immune systems. Global efforts to control the disease have had limited success, and no vaccine has yet been approved for clinical use. Therefore, there is an urgent, unmet need to discover new vaccine candidates. A vaccine against childhood malaria is a priority because children below the age of 5 years are highly vulnerable to the disease. In recent studies, our laboratory discovered Schizont Egress Antigen-1 (PfSEA-1), a 244-kDa-parasite antigen that is crucial for parasite egress from an infected red blood cell (iRBC), which was published as a comprehensive, full-length Research Article in Science. In a parallel approach, we have screened phage display cDNA libraries constructed from parasites isolated at our Tanzanian field site with/without culture adaptation using positive selection with antibodies pooled from resistant two-year-olds and negative selection with antibodies pooled from susceptible children. We identified several independent cDNA clones encoding plasmodium falciparum glutamic acid reach protein (PfGARP) and plant-like calcium-dependent protein kinase (PfCDPK5) that were uniquely recognized by antibodies in resistant, but not susceptible sera. Our preliminary data demonstrate that PfGARP and PfCDPK5 is critical for parasite development in side RBC and egress respectively). PfGARP expresses on the surface of the trophozoite infected RBC and PfCDPK5 is expressed by merozoites as they rupture from erythrocytes. Antibodies against PfGARP and PfCDPK5 block parasite growth up to 99% in vitro, and ortholog vaccine of CDPK5 protect mice from parasitemia, and extend the survival of mice challenged with lethal P. berghei ANKA. Our vaccine discovery program has also identified several known invasion ligands (MSP-4 and MSP-7 collectively referred to as MSPs) In this application, we will evaluate these vaccine candidates with CDPK5 as single fusion protein (PfCDPK5-MSP4 & PfCDPK5-MSP7) in combination with PfGARP in in vitro assays and using multiple adjuvant systems in murine vaccine trials. The lead fusion antigen will be further evaluated for cell mediated immune response using TFRS depletion method in murine model. The deliverables from this study will be an adjuvant optimized tri-valent vaccine ready for Aotus/ P. falciparum challenge and Phase-1 clinical trial in human that targets the entry, intracellular development, and the exit of the parasite cycle in .


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: 2025 ( Subtotal = $363,749 )
2025	2025	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	000	5	11/6/2024	NON-COMPETING CONTINUATION	$363,749
														Subtotal = $363,749

Issue Date FY: 2024 ( Subtotal = $375,000 )
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	000	4	11/22/2023	NON-COMPETING CONTINUATION	$336,844
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	002	4	5/17/2024	NON-COMPETING CONTINUATION	$37,500
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	001	4	2/2/2024	NON-COMPETING CONTINUATION	$656
														Subtotal = $375,000

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	002	3	12/12/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	001	3	10/12/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$273,400
2023	2021	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	2	10/12/2022	NON-COMPETING CONTINUATION	-$273,400
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $368,800 )
2022	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	001	3	3/23/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$368,800
2022	2021	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	2	3/23/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $368,800

Issue Date FY: 2021 ( Subtotal = $406,250 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	2	11/30/2020	NON-COMPETING CONTINUATION	$406,250
														Subtotal = $406,250

Issue Date FY: 2020 ( Subtotal = $400,000 )
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	1	12/13/2019	NEW	$400,000
														Subtotal = $400,000

Grand Total All Awards = $1,913,799

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Multi-target blood stage vaccine against Plasmodium falciparum

Award Number: R01AI144014

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: 12/13/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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