# Multi-target blood stage vaccine against Plasmodium falciparum

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $400,000

## Abstract

Project Summary
 The overall aim of this application is to advance PfCDPK5 and PfGARP as vaccine candidates for
falciparum malaria. P.falciparum malaria affects almost one-half of the world's population and causes more
than 500,000 deaths annually. Young children in malaria endemic areas of Africa have the highest mortality
rate because of their immature immune systems. Global efforts to control the disease have had limited
success, and no vaccine has yet been approved for clinical use. Therefore, there is an urgent, unmet need to
discover new vaccine candidates. A vaccine against childhood malaria is a priority because children below the
age of 5 years are highly vulnerable to the disease. In recent studies, our laboratory discovered Schizont
Egress Antigen-1 (PfSEA-1), a 244-kDa-parasite antigen that is crucial for parasite egress from an infected red
blood cell (iRBC), which was published as a comprehensive, full-length Research Article in Science.
 In a parallel approach, we have screened phage display cDNA libraries constructed from parasites
isolated at our Tanzanian field site with/without culture adaptation using positive selection with antibodies
pooled from resistant two-year-olds and negative selection with antibodies pooled from susceptible children.
We identified several independent cDNA clones encoding plasmodium falciparum glutamic acid reach protein
(PfGARP) and plant-like calcium-dependent protein kinase (PfCDPK5) that were uniquely recognized by
antibodies in resistant, but not susceptible sera. Our preliminary data demonstrate that PfGARP and PfCDPK5
is critical for parasite development in side RBC and egress respectively). PfGARP expresses on the surface of
the trophozoite infected RBC and PfCDPK5 is expressed by merozoites as they rupture from erythrocytes.
Antibodies against PfGARP and PfCDPK5 block parasite growth up to 99% in vitro, and ortholog vaccine of
CDPK5 protect mice from parasitemia, and extend the survival of mice challenged with lethal P. berghei ANKA.
 Our vaccine discovery program has also identified several known invasion ligands (MSP-4 and MSP-7
collectively referred to as MSPs) In this application, we will evaluate these vaccine candidates with CDPK5 as
single fusion protein (PfCDPK5-MSP4 & PfCDPK5-MSP7) in combination with PfGARP in in vitro assays and
using multiple adjuvant systems in murine vaccine trials. The lead fusion antigen will be further evaluated for
cell mediated immune response using TFRS depletion method in murine model. The deliverables from this study
will be an adjuvant optimized tri-valent vaccine ready for Aotus/ P. falciparum challenge and Phase-1 clinical
trial in human that targets the entry, intracellular development, and the exit of the parasite cycle in .

## Key facts

- **NIH application ID:** 9886984
- **Project number:** 1R01AI144014-01A1
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Dipak Kumar Raj
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2019-12-13 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886984

## Citation

> US National Institutes of Health, RePORTER application 9886984, Multi-target blood stage vaccine against Plasmodium falciparum (1R01AI144014-01A1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9886984. Licensed CC0.

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