Natural History of Marburg Virus Infection to Support Medical Countermeasure Development
Jason E. Comer,
Trevor Brasel,
Shane Massey,
David W. Beasley,
Chris M. Cirimotich,
Daniel C. Sanford,
Ying-Liang Chou,
Nancy A. Niemuth,
Joseph Novak,
Carol L. Sabourin,
Michael Merchlinsky,
James P. Long,
Eric J. Stavale,
Daniel N. Wolfe
Affiliations
Jason E. Comer
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
Trevor Brasel
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
Shane Massey
Institutional Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
David W. Beasley
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
Chris M. Cirimotich
Battelle Biomedical Research Center, West Jefferson, OH 43162, USA
Daniel C. Sanford
Battelle Biomedical Research Center, West Jefferson, OH 43162, USA
Ying-Liang Chou
Battelle Biomedical Research Center, West Jefferson, OH 43162, USA
Nancy A. Niemuth
Battelle Biomedical Research Center, West Jefferson, OH 43162, USA
Joseph Novak
AmplifyBio, West Jefferson, OH 43162, USA
Carol L. Sabourin
Tunnell Government Services, Inc., Supporting Biomedical Advanced Research & Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), U.S. Department of Health and Human Services (DHHS), Washington, DC 20201, USA
Michael Merchlinsky
CBRN Vaccines, Biomedical Advanced Research & Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), U.S. Department of Health and Human Services (DHHS), Washington, DC 20201, USA
James P. Long
Tunnell Government Services, Inc., Supporting Biomedical Advanced Research & Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), U.S. Department of Health and Human Services (DHHS), Washington, DC 20201, USA
Eric J. Stavale
CBRN Vaccines, Biomedical Advanced Research & Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), U.S. Department of Health and Human Services (DHHS), Washington, DC 20201, USA
Daniel N. Wolfe
CBRN Vaccines, Biomedical Advanced Research & Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), U.S. Department of Health and Human Services (DHHS), Washington, DC 20201, USA
The Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, recognizes that the evaluation of medical countermeasures under the Animal Rule requires well-characterized and reproducible animal models that are likely to be predictive of clinical benefit. Marburg virus (MARV), one of two members of the genus Marburgvirus, is characterized by a hemorrhagic fever and a high case fatality rate for which there are no licensed vaccines or therapeutics available. This natural history study consisted of twelve cynomolgus macaques challenged with 1000 PFU of MARV Angola and observed for body weight, temperature, viremia, hematology, clinical chemistry, and coagulation at multiple time points. All animals succumbed to disease within 8 days and exhibited signs consistent with those observed in human cases, including viremia, fever, systemic inflammation, coagulopathy, and lymphocytolysis, among others. Additionally, this study determined the time from exposure to onset of disease manifestations and the time course, frequency, and magnitude of the manifestations. This study will be instrumental in the design and development of medical countermeasures to Marburg virus disease.
