# Developing a barcoded malaria parasite panel to assess broadly neutralizing antibodies

> **NIH NIH R21** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2022 · $239,250

## Abstract

PROJECT SUMMARY
Malaria remains a grave threat to global public health with concern that the limited drugs and vector control
strategies at our disposal are becoming less effective. Recent progress and renewed interest in new vaccines
targeting pathogens, including the Plasmodium falciparum malaria parasite, provide an opportunity to expand
our toolkit to combat the disease. A highly efficacious vaccine for malaria, as for other eukaryotic parasites, has
been elusive. Substantial effort has been invested in development of a pre-erythrocytic vaccine targeting the
sporozoite form of the parasite, resulting in the recent recommendation by the World Health Organization for use
in endemic areas. During the clinical blood-stage of malaria, many of the functional antigens that provide the
parasite pathways for invasion into erythrocytes are known, and some naturally occurring antibodies are
protective. Antigenic diversity and variation, among other factors, poses a major challenge for a broadly-
neutralizing blood-stage vaccine, because many immune-targeted molecules for host cell entry are functionally
redundant and sequence polymorphic. As antigens continue to be tested for immunogenicity, it will become a
high-priority to identify those with the best potential for widespread protection against the breadth of antigenically
diverse malaria parasites found across the world. We propose here to develop a platform for facile assessment
of the broadly-neutralizing potential of anti-parasite antibodies. In Step 1, we will identify culture-adapted P.
falciparum clonal lines that represent all major alleles of the parasite globally; and implement state-of-the-art
CRISPR-Cas9 methodologies to introduce short, stably expressed barcode sequences to distinguish the lines.
In Step 2, we will pool 90 barcoded lines and validate the use of Illumina-based amplicon-sequencing to
deconvolute pools and measure the relative levels of the parasite lines. In Step 3, we will use the pooled assay
to measure the strain-specificity of invasion inhibition and broadly-neutralizing potential of monoclonal antibodies
targeting two antigens of interest for a blood-stage vaccine.
 The combination of population genomics, reverse genetic modification of parasites, and quantitative high-
throughput sequencing, will permit us to analyze the functional outcomes of antigenic diversity at unprecedented
scale and complexity; and will transform efforts to identify the most promising antigens for a potent, broadly-
neutralizing malaria vaccine. We further anticipate that the approach will also be useful for non-vaccine related
studies for P. falciparum, including analysis of parasite resistance to antimalarials.

## Key facts

- **NIH application ID:** 10511052
- **Project number:** 1R21AI171658-01
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Manoj T Duraisingh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $239,250
- **Award type:** 1
- **Project period:** 2022-06-29 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10511052

## Citation

> US National Institutes of Health, RePORTER application 10511052, Developing a barcoded malaria parasite panel to assess broadly neutralizing antibodies (1R21AI171658-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10511052. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*