# Liver resident memory for malaria

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $27,718

## Abstract

ABSTRACT
Our R01 project supports NIAID’s mission to better understand, treat, and prevent infectious diseases by focusing on
pre-erythrocytic malaria vaccine development. Vaccines that efficiently stop the Plasmodium sporozoite (spz) or liver
stage provide complete protection against malarial disease and will enable eradication efforts. There are currently no
FDA-approved malaria vaccines for use in humans although repeated dosing with intravenously-administered attenuated
spz has shown sterile protection against challenge in multiple Phase 1-2 clinical trials. Recently, CD8+ T cells that reside
in the liver (liver resident memory T cells or Trm cells) have been identified as key cell types in protection against liver
stage infection. Vaccine strategies that increase liver Trm cells and can be readily adapted to clinical use are therefore
critically needed. Such vaccines could bolster CD8+ T cell immunity and may result in T cell-focused vaccines that
achieve durable, high-grade protection for persons in endemic and non-endemic regions. Our laboratory has developed a
two-dose vaccine that increases liver Trm cells and achieves sterile protection. This approach requires only a single dose
of spz. This project aims to provide pre-clinical support for development of this two-dose ‘prime-and-trap’ vaccine. The
University of Washington (UW) will collaborate with established partners at Sanaria Inc. In Aim 1, we will evaluate
biological and technical questions about the proposed vaccine regimen, including dose dependence, effects of spz
cryopreservation, adjuvant effects, interference from pre-existing antibodies, and use of multiple DNA plasmids. In Aim
2, we will investigate the magnitude and degree of antigen spreading following vaccination, a phenomenon that could
enhance protection in the liver. In Aim 3, we will evaluate the prime-and-trap vaccine in the P. knowlesi non-human
primate (NHP) immunization-challenge model and demonstrate Trm cell targeting in a P. falciparum NHP model.
Tolerability and toxicology endpoints will be obtained in NHP studies in preparation for future clinical studies. In
summary, this project will optimize and assess a two-dose prime-and-trap vaccine rationally designed to elicit complete
protection against the Plasmodium liver stage.

## Key facts

- **NIH application ID:** 10428720
- **Project number:** 3R01AI141857-03S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Sean C Murphy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $27,718
- **Award type:** 3
- **Project period:** 2018-11-23 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428720

## Citation

> US National Institutes of Health, RePORTER application 10428720, Liver resident memory for malaria (3R01AI141857-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10428720. Licensed CC0.

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