The role of Marburg virus glycoprotein diversity on epitopes conservation and its impact on effectiveness of vaccines and therapeutic antibodies: A call for one health strategy in vaccines research, development, and coordinated implementation

• MARV-GP MLD shows the highest genetic diversity compared to RBR and FPR regions. • MARV antibody escape mutations were clustering near key GP epitopes. • RBR and FPR functional domains are conserved but host also non-conservative changes. • Several polymorphisms reduce binding affinity of key neutralizing antibodies. • The study findings underscore One Health strategy in vaccines research and design. The Marburg virus (MARV) is a highly lethal zoonotic filovirus that is responsible for sporadic outbreaks of severe viral hemorrhagic fever with high case mortality rate. Despite global investment in the development of vaccine and antibody-based countermeasures targeting the viral glycoprotein (GP), limited data is available on how such immune pressures shape GP genetic diversity and how this diversity is affecting the effectiveness of on-progress vaccines. In this study, we performed an Insilco-analysis of MARV-GP published sequences to investigate patterns of genetic variation under antibody selection and potentially vaccination pressure. Utilizing publicly available full-length GP sequences, we assessed domain-specific diversity, focusing on the mucin-like domain (MLD), receptor-binding region (RBR), and fusion peptide region (FPR). The immunological impacts of amino acid polymorphisms, including potential escape from neutralizing antibodies including MR78 and MR191 were investigated. Results showed that the MLD had disproportionately high diversity, likely due to relaxed structural constraints, potentially reducing GP-based vaccine efficacy. The RBR and FPR were more conserved, but several non-conservative mutations affected antibody binding affinity. Notably, mutations clustered near known epitopes, suggesting antibody-driven selection. This study underscores the importance of continued molecular and immunogenic surveillance that account for MARV-GP diversity, especially in regions prone to immunologic targeting. These results improve current understanding of viral adaptation under immune pressure and inform MARV vaccines and therapeutic antibodies design strategies. Stakeholders of zoonotic diseases, should invest on integrating One Health strategy in the research and development of safe effective vaccines across all hosts of the pathogens to accelerate diseases elimination.