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Longitudinal Antibody Profiles Correlated with Protection from Malaria in Malawi

Award Number: R21AI151459
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: 01/08/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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Longitudinal Antibody Profiles Correlated with Protection from Malaria in Malawi - PROJECT SUMMARY Malaria continues to be responsible for substantial childhood mortality in Africa despite current control efforts. Developing an effective vaccine for malaria elimination is constrained by knowledge gaps in both naturally- acquired and vaccine-induced immunity. Existing vaccine candidates elicit antibodies against the target antigen but the associations between antibody functional activity and level and duration of protection are unknown. Additionally novel blood-stage antigens that could be used in future vaccines aimed at preventing symptomatic malaria have emerged (some are polymorphic), that need to be further investigated. Preferred antigens should elicit antibody functional activity that is: i) boosted with natural infection; ii) long-lasting; iii) correlated with protection; iv) not highly strain-specific, i.e., effective against a diversity of isolates. Our study aims to clarify these unknowns focusing on 12 understudied blood-stage antigens (and the alleles of those polymorphic antigens) to inform selection of antigens that could be potential vaccine candidates. Prior studies of naturally-acquired antibody immunity have largely quantified antibody magnitude to specific proteins and have typically been limited to quantifying immune responses infrequently or at a single time-point. Because the immune profiles of individuals are dynamic and a function of exposure to infection that cannot be synchronized at the beginning of a study, these largely cross-sectional measurements obscure outcomes of interest. Furthermore, prior studies predominantly measured only magnitude of IgG responses; few have assessed the range and breath of functional activities of antibodies, and the impact of antigen polymorphisms on functional antibody activities. The expertise of our study team, combined with access to samples collected during a longitudinal study with intensive follow-up and a comprehensive study approach, provides an opportunity to address these questions and elucidate the importance of these antigens in acquired immunity to malaria. Our study will be based on a cohort of children and adults who were seen monthly over two years in which subjects had repeated clinical and/or sub clinical malaria infections. Studying this cohort will enable us to gain new insights into the durability and boosting over time of functional antibody activity against blood-stage antigens upon natural exposure to malaria. We will also evaluate the cross-reactivity or strain-specificity of functional antibodies against alternative alleles of polymorphic antigens. Finally, we will evaluate antigens (and alleles) against which functional antibody activity is correlated with protection from symptomatic malaria and high density parasitemia, and we will seek signatures of functional responses that can accurately discriminate protected and unprotected subjects. These correlates of protection will provide endpoints for evaluating future vaccines. This may have implications for strategies to improve vaccine efficacy and implementation.


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: 2024 ( Subtotal = -$553 )
2024	2022	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	8/5/2024	NON-COMPETING CONTINUATION	-$553
														Subtotal = -$553

Issue Date FY: 2022 ( Subtotal = $139,593 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	11/30/2021	NON-COMPETING CONTINUATION	$139,593
														Subtotal = $139,593

Issue Date FY: 2021 ( Subtotal = $276,326 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	1/8/2021	NEW	$276,326
														Subtotal = $276,326

Grand Total All Awards = $415,366

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Longitudinal Antibody Profiles Correlated with Protection from Malaria in Malawi

Award Number: R21AI151459

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: 01/08/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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