# Parasite and host cell factors involved in the formation and persistence of Plasmodium vivax hypnozoites

> **NIH AI R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2026 · $667,525

## Abstract

This application is in response to the NIAID RFA-AI-21-075 entitled “Identification and Characterization of
Persistence Mechanisms of Select Protozoan Pathogens”, which explicitly states the study of P. vivax
hypnozoites as a research objective. P. vivax malaria burdens people within a wide global range and is more
pathogenic than previously appreciated. The parasite’s epidemiology and clinical impact is governed by latent
liver stages called hypnozoites, which are the source of relapsing blood stage infection. The molecular regulation
of hypnozoite stage formation, persistence and activation in hepatocytes has until recently remained unstudied,
mainly due to the lack of laboratory tools for this parasite. This has changed of the past ten years with the
development of our robust human liver-chimeric mouse model (FRG huHep mouse) that enables the detailed
analysis of hypnozoite formation and persistence as well the occurrence of relapses and robust in vitro primary
hepatocyte models of infection. In addition, with partners we have recently developed the genetically defined P.
vivax Chesson strain for use in hypnozoite studies, replacing complex field-isolate derived sporozoites for
infection. With these tools, the goals of this application are the identification of the parasite molecular drivers of
hypnozoite formation and persistence and host hepatocyte factors that impact hypnozoite formation and
persistence. We will achieve these goals through three independent but complementary aims. In Aim 1 we will
generate and interrogate hypnozoite gene expression data with emphasis on factors that are known to regulate
quasi-persistence in salivary gland sporozoites. Candidate factors such as AP2 transcription factors, the
eIF2a/IK2/UIS2 translational repression system and the, SAP1 and PUF stress granule mRNA storage system
will undergo comprehensive examination in P. vivax hypnozoites. Implicated factors that might drive and maintain
hypnozoite persistence will then be fun

## Key facts

- **NIH application ID:** 11502986
- **Project number:** 7R01AI172824-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Stefan HI Kappe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $667,525
- **Award type:** 7
- **Project period:** 2023-02-09T00:00:00 → 2028-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11502986

## Citation

> US National Institutes of Health, RePORTER application 11502986, Parasite and host cell factors involved in the formation and persistence of Plasmodium vivax hypnozoites (7R01AI172824-05). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11502986. Licensed CC0.

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