An mRNA vaccine encoding the Ebola virus glycoprotein induces high neutralizing antibody titers and provides strong protection against lethal infections in mouse models

Stromberg, Zachary R.; Silva, Elvia Elizabeth; Johnston, Sara C.; Johnson, Dylan MacGregor; Hall, Dominique; Adjei, Emmanuel F.; Altin, John A.; Abisoye-Ogunniyan, Abisola; Gollott, Travis; He, Wei; Jones, Iris K. A.; Kwilas, Steve; Lund, Sean Joseph; Mead, Heather L.; Nelson, Georgia A.; Ouyang, Lisa; Peters, Sandra K. G.; Schwedler, Jennifer L.; Trecazzi, Caleb Z.; Turner, Matthew W.; Ye, Chunyan; Bradfute, Steven B.; Fischer, Nicholas O.; Hooper, Jay W.; Ladner, Jason T.; Rasley, Amy; Negrete, Oscar A.

doi:10.3389/fimmu.2025.1682418

An mRNA vaccine encoding the Ebola virus glycoprotein induces high neutralizing antibody titers and provides strong protection against lethal infections in mouse models

Journal Article · Mon Jan 05 00:00:00 EST 2026 · Frontiers in Immunology

DOI:https://doi.org/10.3389/fimmu.2025.1682418· OSTI ID:3019978

Stromberg, Zachary R. ^[1]; ^[2]; Johnston, Sara C. ^[3]; ^[2]; Hall, Dominique ^[4]; Adjei, Emmanuel F. ^[5]; Altin, John A. ^[6]; Abisoye-Ogunniyan, Abisola ^[4]; Gollott, Travis ^[4]; He, Wei ^[4]; Jones, Iris K. A. ^[2]; Kwilas, Steve ^[3]; Lund, Sean Joseph ^[2]; Mead, Heather L. ^[6]; Nelson, Georgia A. ^[6]; Ouyang, Lisa ^[2]; Peters, Sandra K. G. ^[4]; Schwedler, Jennifer L. ^[2]; Trecazzi, Caleb Z. ^[4]; Turner, Matthew W. ^[1] more »

Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sandia National Laboratories (SNL-CA), Livermore, CA (United States)
U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States)
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Northern Arizona Univ., Flagstaff, AZ (United States)
Translational Genomics Research Institute (TGen), Flagstaff, AZ (United States)
Univ. of New Mexico, Albuquerque, NM (United States)
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); Univ. of California, Merced, CA (United States)

Ebola virus (EBOV) is the causative agent of Ebola disease (EBOD), a viral hemorrhagic fever with a notably high case fatality rate. Current treatments for EBOD are limited to monoclonal antibodies or two licensed viral vector vaccines, a recombinant vesicular stomatitis virus (rVSV)-vectored vaccine or an adenovirus and modified vaccinia Ankara regimen. However, comparisons of protection, efficacy, and durability with alternative nucleotide platforms remain understudied. Here, we evaluated the immunogenicity of an mRNA vaccine expressing the EBOV glycoprotein (GP) in parallel with rVSV- and DNA-based vaccine platforms. The mRNA EBOV-GP vaccine, formulated in lipid nanoparticles, elicited significantly higher levels of total IgG and neutralizing antibody titers compared to the rVSV-EBOV-GP vaccine. Linear antibody epitope analysis indicated a preference for targeting the mucin-like domain in EBOV-GP1 following rVSV-based vaccination, while the mRNA platform distinctly targeted the internal fusion loop of EBOV-GP2. After characterizing the immunogenicity of the mRNA vaccine, two models of EBOD were used to demonstrate its protective efficacy: a surrogate rVSV-based challenge model of EBOD using type-I interferon deficient C57BL/6 mice and infection of BALB/c mice with authentic mouse-adapted EBOV. In both studies, the EBOV mRNA vaccine fully protected the mouse cohorts against morbidity and mortality. Additionally, the EBOV mRNA vaccine produced greater neutralizing antibody titers compared to the DNA EBOV-GP vaccine. These results suggest that an mRNA vaccine expressing EBOV-GP can induce robust, functional humoral responses that are protective against EBOD, warranting further development as an alternative to, or as part of a vaccine strategy including, viral vectored vaccines.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Sandia National Laboratories (SNL-CA), Livermore, CA (United States)

Sponsoring Organization:: Defense Threat Reduction Agency (DTRA); USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC05-76RL01830; NA0003525

Other Award/Contract Number:: HDTRA1242031

OSTI ID:: 3019978

Alternate ID(s):: OSTI ID: 3020864

Report Number(s):: PNNL-SA--215597; SAND--2026-17608J; 1784497

Journal Information:: Frontiers in Immunology, Journal Name: Frontiers in Immunology Journal Issue: 1682418 Vol. 16; ISSN 1664-3224

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

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