One-for-one or one-for-all? Considerations for filovirus vaccine development

Abstract

Almost six decades ago, filoviruses were identified as the causative agents of hemorrhagic disease outbreaks in humans. Despite the fact that these diseases have high fatality rates, only countermeasures against one filovirus, Ebola virus (EBOV), have been approved to date [1]. Filovirus outbreaks are thought to originate through spillover from bats, which have been suggested as the filovirus reservoir, to intermediate hosts or end hosts like humans, mostly in remote locations in Africa [2]. Although this occurs infrequently and most outbreaks are small, large outbreaks were reported in 2014 and 2020. From December 2013 until 2016, EBOV devastated the fragile healthcare infrastructure in Guinea, Liberia and Sierra Leone with over 28,000 cases and over 11,000 fatalities [3]. Single cases were imported to other countries, including Nigeria, Mali, Italy, Spain, the United Kingdom and the United States of America (USA); in the USA EBOV transmission occurred from the imported case to healthcare workers [3, 4]. In 2018–2020, the Democratic Republic of the Congo (DRC) reported its 10th—and, to date, largest—EBOV outbreak, with 3,470 cases and 2,287 fatalities [3]. Since 2021, the filoviruses Sudan virus (SUDV) and Marburg virus (MARV) have also garnered global attention, causing outbreaks of hemorrhagic disease: SUDV in Uganda (2022, 2025) [3], and MARV in Guinea (2021), Ghana (2022), Equatorial Guinea (2023), Tanzania (2023) and Rwanda (2024) [5]. MARV is particularly concerning, as its most recent spillovers suggest the expansion of its endemic area into regions where other filoviruses, like EBOV, SUDV and Bundibugyo virus (BDBV), are already endemic. The 2014–2016 EBOV epidemic highlighted another underrecognized aspect of filovirus disease—viral persistence and recrudescence. Growing evidence shows that EBOV and MARV can be sexually transmitted by disease survivors [2]. Vaccination of sexual partners of survivors or treatment of the survivors themselves should therefore be considered. Together, these issues highlight the need for deployable countermeasures and mitigation strategies to temper future outbreaks. Where do we stand today?