# Integrating human and non-human primate data to understand the acquisition of pre-erythrocytic immunity in the face of previous malaria exposure

> **NIH NIH U01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $1,028,550

## Abstract

ABSTRACT
Pre-erythrocytic (PE) malaria vaccines that completely prevent infection in malaria non-endemic regions have
often failed to achieve equally high-level protection when tested in endemic regions. Data from animal models
and humans has identified certain factors that may be contributing to this difference. Active or previous
Plasmodium infections rank highly amongst these factors because infection is known to significantly impact
innate and adaptive immune responses to malaria vaccines. We hypothesize that previous malaria exposure is
a key driver of the suboptimal immunity observed in clinical trials of PE vaccines in endemic areas. However, a
full assessment of how such conditions affect pre-erythrocytic immune responses is lacking in large part
because much of the protective immune repertoire against PE malaria exists as tissue resident memory T cells
in the liver, which is inaccessible in human clinical trials. Here, we propose to address this question of malaria
vaccine hyporesponsiveness in endemic regions by performing vaccine studies in previously-infected versus
naïve non-human primates (NHP) where we can study the tissue-specific response down to the single cell
level and integrate these with data from peripheral blood samples from similarly-vaccinated human clinical trial
participants in endemic and non-endemic regions. Our exhaustive studies in NHPs will be specifically guided
by hypotheses derived directly from human data. The emerging high-density data will then be used to identify
mechanisms, build models and formulate concrete hypotheses that can then be validated across a number of
clinical trial samples with the overall goal of elucidating patterns or biomarkers that map with protection/lack of
protection and immunogenicity/lack of immunogenicity in malaria-naïve and -experienced volunteers. Thus, we
aim to: 1) define protective liver-resident PE immunity at the single cell level; 2) identify the mechanisms by
which previous malaria exposure impacts baseline and innate immunity; 3) build models of the complex
interplay between baseline, innate, and adaptive immunity and; 4) use these to identify strategies to overcome
hyporesponsiveness to PE vaccines in endemic areas. This U01 project combines an inter-institutional, inter-
disciplinary team of basic, translational, and clinical scientists from within and outside malaria whose unique
expertise, resources, and collaborative style will create breakthroughs insights about this highly complex yet
critically important vaccine challenge.

## Key facts

- **NIH application ID:** 10769823
- **Project number:** 5U01AI165457-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Sean C Murphy
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,028,550
- **Award type:** 5
- **Project period:** 2022-02-10 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769823

## Citation

> US National Institutes of Health, RePORTER application 10769823, Integrating human and non-human primate data to understand the acquisition of pre-erythrocytic immunity in the face of previous malaria exposure (5U01AI165457-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10769823. Licensed CC0.

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