Postexposure Treatment of Marburg Virus Infection | CDC EID

EID Journal Home > Volume 16, Number 7–July 2010

Volume 16, Number 7–July 2010
Dispatch
Postexposure Treatment of Marburg Virus Infection
Thomas W. Geisbert, Lisa E. Hensley, Joan B. Geisbert, Anders Leung, Joshua C. Johnson, Allen Grolla, and Heinz Feldmann
Author affiliations: National Emerging Infectious Diseases Laboratories Institute, Boston, Massachusetts, USA (T.W. Geisbert, J.B. Geisbert); US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA (L.E. Hensley, J.C. Johnson); Public Health Agency of Canada, Winnipeg, Manitoba, Canada (A. Leung, A. Grolla); and National Institutes of Health, Hamilton, Montana, USA (H. Feldmann)

Suggested citation for this article

Abstract
Rhesus monkeys are protected from disease when a recombinant vesicular stomatitis virus–based vaccine is administered 20–30 min after infection with Marburg virus. We protected 5/6 monkeys when this vaccine was given 24 h after challenge; 2/6 animals were protected when the vaccine was administered 48 h postinfection.

The filoviruses, Marburg virus (MBGV) and Ebola virus (EBOV), have been associated with sporadic episodes of hemorrhagic fever (HF) in Central Africa that produce severe disease and high mortality rates among infected patients (1). MBGV and EBOV are also considered potential biological weapons. No approved active or passive therapeutic modalities exist for filovirus infections. Although much progress has been made in developing preventive vaccines that can protect nonhuman primates against lethal challenge with MBGV and EBOV, advances in development of postexposure interventions against the filoviruses have not kept pace. Some degree of success has been achieved by using strategies that mitigate the coagulation abnormalities characterizing filoviral infection (2,3). Also, new postexposure treatment approaches, based on small interfering RNA (4) and antisense oligomers (5,6), have shown promising results in rodent models, but no reports have been published of evaluations of either strategy in the more stringent macaque models.

Recently, we showed the first complete postexposure protection of nonhuman primates against a filovirus by administering a live-attenuated recombinant vesicular stomatitis virus (rVSV) vaccine vector expressing the MBGV glycoprotein (GP) (VSVΔG MBGV GP) shortly after a high-dose MBGV challenge (7,8). We demonstrated that an rVSV vector, expressing the Zaire EBOV (ZEBOV) GP, protected 50% of rhesus macaques when administered shortly after a high-dose ZEBOV challenge (9). We further showed that an rVSV vector expressing the Sudan EBOV GP completely protected rhesus monkeys from a lethal challenge with this virus when administered shortly after exposure (10). All animals in these 3 studies were treated once with rVSV vectors 20–30 min after filovirus challenge. The primary question raised from these investigations is how far out treatment can be delayed before there is no survival or beneficial effect. Using a homologous VSVΔG MBGV GP vector, we have delineated a window of opportunity for treatment of MBGV-infected rhesus macaques.

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Suggested Citation for this Article
Geisbert TW, Hensley LE, Geisbert JB, Leung A, Johnson JC, Grolla A, et al. Postexposure treatment of Marburg virus infection. Emerg Infect Dis [serial on the Internet]. 2010 Jul [date cited]. http://www.cdc.gov/EID/content/16/7/1119.htm

DOI: 10.3201/eid1607.100159