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Integrating human and non-human primate data to understand the acquisition of pre-erythrocytic immunity in the face of previous malaria exposure

Award Number: U01AI165457
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Pre-erythrocytic (PE) malaria vaccines that completely prevent infection in malaria non-endemic regions have often failed to achieve equally high-level protection when tested in endemic regions. Data from animal models and humans has identified certain factors that may be contributing to this difference. Active or previous Plasmodium infections rank highly amongst these factors because infection is known to significantly impact innate and adaptive immune responses to malaria vaccines. We hypothesize that previous malaria exposure is a key driver of the suboptimal immunity observed in clinical trials of PE vaccines in endemic areas. However, a full assessment of how such conditions affect pre-erythrocytic immune responses is lacking in large part because much of the protective immune repertoire against PE malaria exists as tissue resident memory T cells in the liver, which is inaccessible in human clinical trials. Here, we propose to address this question of malaria vaccine hyporesponsiveness in endemic regions by performing vaccine studies in previously-infected versus naïve non-human primates (NHP) where we can study the tissue-specific response down to the single cell level and integrate these with data from peripheral blood samples from similarly-vaccinated human clinical trial participants in endemic and non-endemic regions. Our exhaustive studies in NHPs will be specifically guided by hypotheses derived directly from human data. The emerging high-density data will then be used to identify mechanisms, build models and formulate concrete hypotheses that can then be validated across a number of clinical trial samples with the overall goal of elucidating patterns or biomarkers that map with protection/lack of protection and immunogenicity/lack of immunogenicity in malaria-naïve and -experienced volunteers. Thus, we aim to: 1) define protective liver-resident PE immunity at the single cell level; 2) identify the mechanisms by which previous malaria exposure impacts baseline and innate immunity; 3) build models of the complex interplay between baseline, innate, and adaptive immunity and; 4) use these to identify strategies to overcome hyporesponsiveness to PE vaccines in endemic areas. This U01 project combines an inter-institutional, inter- disciplinary team of basic, translational, and clinical scientists from within and outside malaria whose unique expertise, resources, and collaborative style will create breakthroughs insights about this highly complex yet critically important vaccine challenge.


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: 2023 ( Subtotal = $1,028,550 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	2	1/26/2023	NON-COMPETING CONTINUATION	$1,028,550
2023	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	1	12/7/2022	NEW	$0
														Subtotal = $1,028,550

Issue Date FY: 2022 ( Subtotal = $1,028,550 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	1	2/10/2022	NEW	$1,028,550
														Subtotal = $1,028,550

Grand Total All Awards = $2,057,100

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Integrating human and non-human primate data to understand the acquisition of pre-erythrocytic immunity in the face of previous malaria exposure

Award Number: U01AI165457

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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