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Divergent antibody recognition profiles are generated by protective mRNA vaccines against Marburg and Ravn viruses
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Divergent antibody recognition profiles are generated by protective mRNA vaccines against Marburg and Ravn viruses
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Journal Article
Divergent antibody recognition profiles are generated by protective mRNA vaccines against Marburg and Ravn viruses
2025
Overview
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.
No approved vaccines are available against Marburg virus. In this study, the authors developed mRNA vaccines against Marburg virus and the related Ravn virus and show that they induce robust antibody response and provide protection against homologous and heterologous viruses in guinea pigs.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/31
/ 13/51
/ 14
/ 14/63
/ 42
/ 64
/ 9/10
/ Animals
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ Antigens
/ Binding
/ Female
/ Glycan
/ Humanities and Social Sciences
/ Humans
/ Licenses
/ Lipids
/ Marburg Virus Disease - immunology
/ Marburg Virus Disease - prevention & control
/ Marburg Virus Disease - virology
/ mRNA
/ Science
/ Severe acute respiratory syndrome coronavirus 2
/ Vaccines
/ Vaccines, Synthetic - immunology
/ Viruses
