# Defining the effect of Plasmodium infection on Ebola virus vaccine efficacy

> **NIH NIH UH2** · UNIVERSITY OF IOWA · 2024 · $194,375

## Abstract

PROJECT SUMMARY
Zaire Ebola virus (EBOV) infections remain an emerging threat in Central and West Africa with case fatality rates
reaching as high as 90%. An FDA-approved, live-attenuated, recombinant vaccine called ERVEBO has shown
promise during recent outbreaks in Guinea in 2016 and Democratic Republic of the Congo (DRC) in 2019.
ERVEBO stimulates antibody responses directed against the EBOV glycoprotein (GP). “Ring vaccination” is the
current emergency immunization strategy that focuses on immunizing direct contacts and geographically
proximal populations surrounding the epicenter of an EBOV outbreak. However, emerging data in the DRC show
that ring vaccination can be highly porous; nearly 30% of EBOV-infected participants in a recent antiviral trial in
the DRC were prior recipients of the ERVEBO vaccine. The mechanistic bases for these vaccine failures are not
known.
 This multi-PI, interdisciplinary project explores the hypothesis that acute malaria impairs EBOV
immunization-induced B and T cell responses. In support of this hypothesis, EBOV outbreaks largely occur
where Plasmodium falciparum infections are endemic; malaria is common throughout Central and West Africa.
Moreover, our collaborative team has developed experimental Plasmodium infection and EBOV vaccination
systems to generate preliminary data showing that malaria dramatically impairs EBOV vaccine-induced, virus-
specific antibody responses. We have also identified potential strategies to overcome the malaria-associated
impairments in vaccine efficacy. In this project we synergistically apply tractable, high-resolution, antigen-specific
systems to determine the mechanisms by which Plasmodium infections impact EBOV vaccine-induced humoral
and cellular immunity. These new approaches facilitate our long-term goal to define the impact of Plasmodium
infection on the efficacy of EBOV vaccine-induced immune responses. Our goal is addressed by three specific
aims that test: 1) how Plasmodium infections impact vaccine-induced, virus specific B cell responses; 2) how
Plasmodium infections influence the function of helper T cell subsets required for promoting antibody responses;
and 3) how malaria affects EBOV vaccine-induced protection against virulent mouse adapted, BSL-4 EBOV
challenge. Successful completion of these studies will reveal the mechanisms by which Plasmodium infections
impair EBOV vaccine responses and provide clinically applicable approaches to overcome this impairment. Such
knowledge gained will inform vaccine strategies that must be rapidly and effectively implemented during EBOV
outbreaks.

## Key facts

- **NIH application ID:** 10906240
- **Project number:** 5UH2AI174415-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Noah Sullivan Butler
- **Activity code:** UH2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2023-08-11 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906240

## Citation

> US National Institutes of Health, RePORTER application 10906240, Defining the effect of Plasmodium infection on Ebola virus vaccine efficacy (5UH2AI174415-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10906240. Licensed CC0.

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