Divergent antibody recognition profiles are generated by protective mRNA vaccines against Marburg and Ravn viruses

Michelle Meyer, Bronwyn M. Gunn, Colette Pietzsch, Chandru Subramani, Kritika Kedarinath, Paula P. Villarreal, Matthew A. Hyde, Erica Ollmann Saphire, James E. Crowe, Galit Alter, Sunny Himansu, Andrea Carfi () and Alexander Bukreyev ()
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Michelle Meyer: University of Texas Medical Branch
Bronwyn M. Gunn: Washington State University
Colette Pietzsch: University of Texas Medical Branch
Chandru Subramani: University of Texas Medical Branch
Kritika Kedarinath: University of Texas Medical Branch
Paula P. Villarreal: University of Texas Medical Branch
Matthew A. Hyde: Galveston National Laboratory
Erica Ollmann Saphire: La Jolla Institute for Immunology
James E. Crowe: Vanderbilt University Medical Center
Galit Alter: MIT and Harvard
Sunny Himansu: Moderna Inc.
Andrea Carfi: Moderna Inc.
Alexander Bukreyev: University of Texas Medical Branch

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract The first-ever recent Marburg virus (MARV) outbreak in Tanzania and recent emergences in Rwanda, Ghana and Equatorial Guinea underscore the importance of therapeutic or vaccine development against the virus, for which none are approved. mRNA vaccines were proven successful in a pandemic-response to severe acute respiratory syndrome coronavirus-2, making it an appealing platform to target pathogenic emerging viruses. Here, we develop 1-methyl-pseudouridine-modified mRNA vaccines formulated in lipid nanoparticles (LNP) targeting the glycoproteins (GP) of MARV and the closely-related Ravn virus (RAVV). Vaccination of female guinea pigs elicits robust binding and neutralizing antibodies and confers complete protection against homologous and heterologous virus replication, disease and death. Characterization of antibody responses identifies disparities in the binding and functional profiles between the two viruses and regions in GP that are broadly reactive. The glycan cap is highlighted as an immunoreactive site for orthomarburgviruses, inducing antibody responses that are virus dependent. Profiling the antibody responses against the two viruses provides insight into how antigenic differences may affect the response towards conserved GP regions, which would otherwise be predicted to be cross-reactive, and has implications for the future design of broadly protective vaccines. The results support the use of mRNA-LNPs against pathogens of high consequence.

Date: 2025
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DOI: 10.1038/s41467-025-60057-0

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