# Defining clinical and sterile immunity to Plasmodium falciparum infection using systems biology approaches

> **NIH NIH K08** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $185,224

## Abstract

Project Summary/Abstract
 Malaria afflicts ~198 million people yearly, with 438,000 malaria deaths due to Plasmodium falciparum,
underscoring the need for a highly effective malaria vaccine. The first licensed malaria vaccine, RTS,S, may
provide much-needed reductions in morbidity and mortality, but its modest efficacy in reducing clinical malaria
in the target population of African infants leaves ample margin for improvement. A better understanding of
immunity to P. falciparum in naturally exposed populations can inform efforts to improve malaria vaccine
design. To date, there are no reliable correlates of protection from either symptomatic P. falciparum infection
(clinical immunity) or parasitemia (sterile immunity). Systems biology utilizes computational modeling of large-
scale data sets to elucidate complex biological networks and has the potential to reveal novel predictors and
mechanisms of malaria protection when applied to well-designed clinical cohort studies.
 In this project, the candidate proposes to assess immune predictors of natural protection from P. falciparum
infection using systems biology approaches. By analyzing clinical data and blood specimens collected from a
well-characterized, prospective cohort of Malian children who differ in their degree of immunity to P. falciparum
infection, the candidate will address two main research aims: 1) determine immune parameters predictive of
protection from symptomatic infection (clinical immunity) and protection from P. falciparum infection (sterile
immunity) and 2) relate these immune parameters and outcomes to the ability of plasma obtained from these
children to inhibit parasite invasion into liver and red blood cells in vitro. The practical implications of this work
include identifying novel immune predictors and mechanisms of protection from P. falciparum infection and
disease within the vaccine target population that could provide rational benchmarks for candidate malaria
vaccines.
 The candidate is firmly committed to a career in translational malaria research and systems biology and is
strongly supported in his career and research goals by his mentors and his division at the Indiana University
School of Medicine. He currently holds a position as an Assistant Professor of Medicine with 80% protected
time for research, independent laboratory and office space, and funding for equipment. The current proposal
includes a comprehensive mentorship and didactic plan to advance the candidate's skills and knowledge in
biostatistics and computational biology required for developing expertise in systems biology. Under the
guidance of his primary mentor, Dr. Chandy John, and his co-mentors, Dr. Wanzhu Tu, Dr. Lang Li, and Dr.
Peter Crompton, he will advance his bioinformatics skills and learn predictive modeling methodologies that will
be directly applied to this proposal. Completion of this comprehensive training plan will provide the candidate
with the skills and experience necessary to bec...

## Key facts

- **NIH application ID:** 9854874
- **Project number:** 5K08AI125682-04
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Tuan Manh Tran
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,224
- **Award type:** 5
- **Project period:** 2017-02-10 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854874

## Citation

> US National Institutes of Health, RePORTER application 9854874, Defining clinical and sterile immunity to Plasmodium falciparum infection using systems biology approaches (5K08AI125682-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9854874. Licensed CC0.

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