# The Kinetics and Dynamics of Functional Immune Responses to Plasmodium falciparum Strains

> **NIH NIH F31** · YALE UNIVERSITY · 2024 · $48,974

## Abstract

Project Summary/Abstract
Malaria caused by Plasmodium falciparum remains a leading cause of death primarily in children under the age
of five in Sub-Saharan Africa. Despite being treatable with chemotherapy, the global spread of drug resistance,
along with the lack of natural sterilizing immunity and a vaccine with only modest efficacy has made the goal of
malaria elimination an ever more distant goal. Identification of highly conserved antigen targets that prove to be
true correlates of immune protection would create transformational tools in malaria research. To do this, there
is need for a better understanding of the mechanisms underlying the development of immunity to malaria. This
proposal will focus on understanding the kinetics and dynamics of functional immune responses to merozoite
antigens longitudinally and with consideration to natural genetic diversity of currently circulating parasite
genotypes. With defined immune correlates of protection not yet broadly established in malaria, it is essential to
move beyond antibody-antigen recognition and towards a better understanding of antibody-mediated
mechanisms of functional immune responses. The blood-stage of malaria represents an attractive target as it is
responsible for both clinical disease severity and onward transmission and previous studies have demonstrated
that antibodies against P. falciparum antigens play a critical role in controlling blood-stage infection. The first
objective is to quantify anti-merozoite functional activity by assessing mechanisms that are associated with
protective blood-stage immune responses including neutralization and opsonic phagocytosis. Extensive
consideration for the development of the next malaria vaccine needs to understand the extent of genetic diversity
on protective functional immune responses. A second objective is to understand how merozoite antigenic
diversity affects functional immune responses by quantifying the degree to which functional opsonizing and
neutralizing immune responses are strain-specific or strain-transcendent when challenged with strains of varying
degrees of genomic relatedness. To evaluate these objectives, we will use serum samples collected
longitudinally following a genomically well-characterized malaria infection and P. falciparum parasite isolates
from these day 0 infections from a Senegalese cohort. The central hypothesis is that functional immune
responses against P. falciparum are developed through changes in antibody composition over the course of
infection, with broadly functionally protective responses dependent on the degree of parasite genomic and
genetic relatedness. Senegal is an ideal setting for understanding the determinants of highly functional immune
responses to key merozoite antigens, as transmission is low, and multiple individuals in the population are
exposed to genomically identical strains and have monogenomic infections. Understanding determinants of
highly functional immune responses and the a...

## Key facts

- **NIH application ID:** 10825746
- **Project number:** 1F31AI176818-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Kelly Hagadorn
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825746

## Citation

> US National Institutes of Health, RePORTER application 10825746, The Kinetics and Dynamics of Functional Immune Responses to Plasmodium falciparum Strains (1F31AI176818-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10825746. Licensed CC0.

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