# Plasmodium vivax Erythrocyte Invasion Mechanisms and Humoral Immune Response in Duffy Negative Africans

> **NIH NIH R01** · UNIVERSITY OF NORTH CAROLINA CHARLOTTE · 2022 · $673,627

## Abstract

PROJECT SUMMARY
Title: Plasmodium vivax Erythrocyte Invasion Mechanisms and Humoral Immune
 Response in Duffy Negative Africans
Individuals of African ancestry were thought to be protected from Plasmodium vivax
because they lack Duffy antigen expression on the surface of their erythrocytes rendering
P. vivax unable to invade their red blood cells. However, an increasing number of P. vivax
cases reported across Africa and in Duffy-negative individuals challenges this
conventional dogma, raising the possibility that some P. vivax lineages have evolved to
use ligands other than Duffy Binding Protein for erythrocyte invasion. The intrinsic
invasion mechanism and immune response of Duffy-negative individuals to P. vivax are
largely unknown. In this application, we will investigate the expression and function
of erythrocyte binding genes in Duffy-negative P. vivax and the antibody response
of Duffy-negative individuals to P. vivax antigens. There are three specific aims: 1) to
identify genes with differential expression between Duffy-positive and Duffy-negative P.
vivax by RNA-seq; 2) to determine in vitro binding and invasion activities of P. vivax
candidate ligand proteins to Duffy-negative red blood cells; and 3) to examine in vivo
antibody levels to targeted P. vivax antigens associated with erythrocyte invasion in Duffy-
negative patients. The proposed research will be conducted in Ethiopia, where malaria is
a major public health problem and about 30% of the 1.2 million confirmed malaria cases
were P. vivax. As our study sites have a large number of P. vivax cases and a
significant proportion of Duffy-negative individuals, we have a unique opportunity
to study the invasion mechanisms of P. vivax in Africa. We have a collaborative team
and logistics in place for sample collection and processing. Our established lab culture
facility closes to the health centers and successful P. vivax transcriptome data obtained
from cultured schizonts have demonstrated the feasibility of this research. Comparison of
P. vivax transcriptomes between Duffy-negative and Duffy-positive individuals from both
in vitro and in vivo samples will provide the first description of genetic and functional
attributes of P. vivax that permit infection of Duffy-negative erythrocytes. This research
will significantly enhance the understanding of invasion mechanism of P. vivax in Duffy-
negative individuals and lay a foundation for molecular and biochemical characterizations
of P. vivax ligand-receptor interactions. Knowledge of P. vivax invasion mechanisms
and host immune responses will have important implications for P. vivax vaccine
development and vivax malaria risk assessment both within and outside Africa.

## Key facts

- **NIH application ID:** 10445540
- **Project number:** 1R01AI162947-01A1
- **Recipient organization:** UNIVERSITY OF NORTH CAROLINA CHARLOTTE
- **Principal Investigator:** Eugenia Lo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $673,627
- **Award type:** 1
- **Project period:** 2022-02-09 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445540

## Citation

> US National Institutes of Health, RePORTER application 10445540, Plasmodium vivax Erythrocyte Invasion Mechanisms and Humoral Immune Response in Duffy Negative Africans (1R01AI162947-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445540. Licensed CC0.

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