# Validation and characterization of antibody responses to Plasmodium falciparum antigens identified by protein array screening

> **NIH NIH R03** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $79,250

## Abstract

PROJECT SUMMARY
Malaria afflicts more than 200 million people yearly, with the malaria parasite Plasmodium falciparum being
responsible for the vast majority of the ~405,000 malaria deaths in 2018. A highly effective malaria vaccine is
widely viewed as a much-needed tool for reducing malaria in endemic areas where healthcare delivery and
vector control strategies are often disrupted by political conflict, natural disasters, and epidemics of rapidly
transmissible viruses. Vaccines that target pre-erythrocytic antigens and whole sporozoite immunization
approaches aim to induce sterile immunity that prevents the progression of liver-stage infection and thus the
establishment of parasitemia and clinical malaria. However, the first licensed malaria vaccine, which targets the
pre-erythrocytic circumsporozoite protein, is only partially effective at preventing severe malaria in African
infants. Inclusion of asexual blood-stage antigens in a multi-stage malaria vaccine could improve the efficacy of
partially effective first-generation vaccines by mitigating clinical disease caused by breakthrough parasitemia.
Several promising blood-stage antigens have been prioritized in clinical trials, but the continued evaluation of
other antigens in the malaria vaccine development pipeline is prudent given the challenges of achieving field
efficacy against a genetically diverse parasite. In our preliminary studies, we found that antibody responses
against two distinct P. falciparum antigens were significantly increased in a subset of malaria-protected children
relative to malaria-susceptible children in a longitudinal cohort study conducted in Mali. We propose to evaluate
these two P. falciparum antigens as malaria vaccine candidates by determining whether naturally acquired IgG
antibodies against these proteins can predict malaria protection in the larger parent cohort and exert anti-
parasitic activity. Our hypothesis is that conserved regions within either antigen are the targets of naturally
acquired protective immunity against falciparum malaria. To test this hypothesis, we will determine the genetic
diversity of local P. falciparum field isolates within the genes encoding these parasite antigens, which will allow
us to identify a conserved region for recombinant protein expression. We will then determine if naturally acquired
antibody responses against the conserved region within each antigen can predict protection from malaria in the
parent cohort study and whether these antibodies have activity against P. falciparum parasites in vitro.
Successful completion of this project will provide insight on the genetic diversity of these two antigens and
provide evidence as to whether conserved regions within these antigens are the targets of naturally acquired
protective immunity against malaria.

## Key facts

- **NIH application ID:** 10195524
- **Project number:** 1R03AI159780-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Tuan Manh Tran
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,250
- **Award type:** 1
- **Project period:** 2021-02-10 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195524

## Citation

> US National Institutes of Health, RePORTER application 10195524, Validation and characterization of antibody responses to Plasmodium falciparum antigens identified by protein array screening (1R03AI159780-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10195524. Licensed CC0.

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