Journal article
Acute malaria dysregulates specialized lymph node macrophages to suppress vaccine-elicited protection against the Ebola virus
mBio, Vol.17(2), e0279625
02/11/2026
DOI: 10.1128/mbio.02796-25
PMCID: PMC12892958
PMID: 41467787
Abstract
The filovirus, Ebola virus (EBOV), causes outbreaks of EBOV disease (EVD) throughout equatorial Africa. ERVEBO is a replication-competent recombinant vesicular stomatitis virus-vectored vaccine encoding the EBOV glycoprotein (recombinant vesicular stomatitis virus [rVSV]/EBOV), which is licensed to control EVD outbreaks. EVD outbreaks occur in regions endemic for
-caused malaria.
infections persist due in part to the parasite's ability to evade sterilizing immunity, which also dampens immune responses to heterologous vaccines. Acute murine
infection at the time of rVSV/EBOV vaccination reduced vaccine-mediated protection against mouse-adapted EBOV (ma-EBOV) challenge. Decreased protection was associated with a
induced interferon gamma-mediated decrease of rVSV/EBOV replication in lymph node macrophages, resulting in reduced primary anti-EBOV glycoprotein antibody responses. Higher doses of rVSV/EBOV partially overcame the antibody deficits and elicited protective responses. Evidence of the negative impact of
on the efficacy of low-dose rVSV/EBOV vaccine protocols supports the use of high antigen loads in the effective management of EVD outbreaks.
We show that a blood-stage murine
infection negatively impacts the primary antibody response elicited by low-dose recombinant vesicular stomatitis virus (rVSV)/Ebola virus (EBOV) vaccination and results in reduced protection against a lethal dose of mouse-adapted EBOV. This defect occurs within the draining lymph node due to the elevation of interferon gamma elicited in
(
-infected mice. The
-imposed decrease in vaccine-mediated protection can be overcome with higher doses of rVSV/EBOV. While the strong protection conferred by rVSV/EBOV and significant side effects known to be associated with this vaccine have led to the suggestion that the vaccine dosage be reduced, our studies provide a rationale for maintaining the current higher dose.
Details
- Title: Subtitle
- Acute malaria dysregulates specialized lymph node macrophages to suppress vaccine-elicited protection against the Ebola virus
- Creators
- Jonah Elliff - University of IowaLindsey Grady - University of IowaKyle L O'Donnell - National Institutes of HealthCaitlin Messingham - University of IowaKai J Rogers - University of IowaJobaida Akther - University of Alabama at BirminghamAndrew Thurman - University of Iowa, Internal MedicineRahul Vijay - Rosalind Franklin University of Medicine and ScienceAlejandro Pezzulo - University of IowaTroy Randall - University of Alabama at BirminghamAndrea Marzi - National Institute of Allergy and Infectious DiseasesNoah S Butler - University of IowaWendy Maury - University of Iowa
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.17(2), e0279625
- DOI
- 10.1128/mbio.02796-25
- PMID
- 41467787
- PMCID
- PMC12892958
- NLM abbreviation
- mBio
- ISSN
- 2150-7511
- eISSN
- 2150-7511
- Publisher
- American Society of Microbiology; WASHINGTON
- Grant note
- National Institutes of Health: R21AI139902
This study was supported by the National Institutes of Health (NIH, USA) grants R21AI139902 and UH2AI174415 to W.M. and N.S.B. N.S.B. was also supported by NIH R01AI1125446, R01AI167058, and R01AI127481. J.A. and T.R. were supported by NIH R01AI152476 and R01AI153413. J.E. was supported by NIH T32AI007485 and F30AI181340-01A1. A.M. and K.L.O. were supported by an Intramural Research Program, NIH award (AI001254) to A.M.
- Language
- English
- Electronic publication date
- 12/30/2025
- Date published
- 02/11/2026
- Academic Unit
- Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9985097024502771
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