Developing Vaccines to Improve Preparedness for Filovirus Outbreaks: The Perspective of the USA Biomedical Advanced Research and Development Authority (BARDA)

Abstract

Outbreaks of viral hemorrhagic fever caused by filoviruses have become more prevalent in recent years, with outbreaks of Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV) all occurring in 2022 and 2023. While licensed vaccines are now available for EBOV, vaccine candidates for SUDV and MARV are all in preclinical or early clinical development phases. During the recent outbreak of SUDV virus disease, the Biomedical Advanced Research and Development Authority (BARDA), as part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, implemented key actions with our existing partners to advance preparedness and enable rapid response to the outbreak, while also aligning with global partners involved in the implementation of clinical trials in an outbreak setting. Beyond pre-existing plans prior to the outbreak, BARDA worked with product sponsors to expedite manufacturing of vaccine doses that could be utilized in clinical trials. While the SUDV outbreak has since ended, a new outbreak of MARV disease has emerged. It remains critical that we continue to advance a portfolio of vaccines against SUDV and MARV while also expediting manufacturing activities ahead of, or in parallel if needed, outbreaks.

Modeling Supply and Demand Dynamics of Vaccines against Epidemic-Prone Pathogens: Case Study of Ebola Virus Disease

“…The modeling framework could be applied to other geographic populations, risk groups, and priority pathogens. Since EBOV serves as a useful prototype pathogen, learnings could be transferred to accelerate progress on vaccine countermeasures against other viruses in the Filoviridae family [ 34 , 129 ]. This includes defining conditions necessary for the sustainability of SUDV or MARV vaccines, as well as evaluating supply and demand tradeoffs when pursuing monovalent versus broadly protective antigens.…”

“…Currently, two vaccines have received WHO pre-qualification against EBOV, while many more are in development for other viruses in the Filoviridae family such as the Sudan species of Ebola (SUDV) and Marburg (MARV) [ 34 ]. Ervebo, initially developed by the Public Health Agency of Canada before being licensed to Merck, is a one-dose replication-competent viral vector vaccine that consists of a live attenuated recombinant vesicular stomatitis virus (rVSV).…”

Bioinformatic, Biochemical, and Immunological Mining of MHC Class I Restricted T Cell Epitopes for a Marburg Nucleoprotein Microparticle Vaccine

“…Unlike Ebola VHFs [ 19 ], there are no licensed vaccines or therapeutics for Marburg virus outbreaks [ 20 ]. While MARV vaccine candidates are in clinical and preclinical testing, they rely on platforms such as attenuated recombinant vesicular stomatitis virus carrying the viral glycoprotein (VSVΔG) [ 21 , 22 ] or the chimpanzee replication-defective adenovirus 3 vector ChAd3-MARV [ 23 , 24 ].…”

How Global Collaboration Can Improve the Medical Countermeasure Life Cycle for Infectious Disease Outbreaks

“…The ERVEBO vaccine, in contrast, presents a potential model for how international partnerships can create a more sustainable MCM ecosystem. A collaboration between the product sponsor, BARDA, and Gavi/UNICEF has led to both a national and international stockpile that reduces the burden on individual governments, supports sustainment of manufacturing, and increases access for the countries that need this product most [ 6 ]. Additional efforts are required, even for this scenario, but the ERVEBO example demonstrates that partnerships can promote sustainability.…”