Ebola virus and Sudan virus infection in humans: a comparison to inform vaccine research and development

Recent outbreaks of Ebola virus (EBOV) disease (EVD) and Sudan virus (SUDV) disease (SVD) in sub-Saharan Africa underscore the ongoing public health threat posed by orthoebolaviruses. While highly effective vaccines are licensed for prevention of EVD, these offer limited cross-protection against other orthoebolaviruses, and no vaccines are licensed for SVD. Candidate SUDV vaccines are in development, but the sporadic nature of SVD outbreaks poses challenges for demonstrating clinical efficacy. In this context, it is important to consider whether and how the extensive evidence generated for EBOV infection, disease, and vaccine development can be leveraged to support SUDV vaccine development, consistent with the WHO prototype pathogen approach. Here, we synthesize available human data on the epidemiology, natural history, pathogenesis, and immunology of EBOV and SUDV infection to delineate their key similarities and differences. EBOV has caused more outbreaks, cases, and deaths than SUDV and has been more geographically widespread. There may be some differences in the typical causes of outbreaks, although gaps remain in understanding animal reservoirs for both viruses. Despite more limited data for SUDV, available evidence indicates that EBOV and SUDV share similar routes and progression of infection in humans, with comparable pathology and clinical presentation. Case fatality rates (CFRs) are generally higher for EVD than SVD. However, CFRs are influenced by outbreak context and healthcare access and should not be interpreted in isolation as evidence of intrinsic viral virulence. Collectively, this synthesis supports continued advancement of SUDV vaccine development using EBOV-informed evidence, while integrating SUDV-specific data where available.