Abstract
Marburg virus (MARV) is the causative agent of hemorrhagic fever outbreaks with high case fatality rates. Closely related to Ebola virus, MARV is a filamentous virus with a negative-sense, single-stranded RNA genome. Although extensive studies on filovirus countermeasures have been conducted, there are no licensed treatments against MARV infections. An experimental vaccine based on the recombinant vesicular stomatitis virus (VSV) expressing the MARV-Musoke glycoprotein demonstrated complete protection when a single dose was administered 28 days and up to 14 months prior to MARV challenge. Here, we analyzed the protective efficacy of an updated vaccine expressing the MARV-Angola glycoprotein (VSV-MARV). A single dose of VSV-MARV given 5 weeks before challenge provided uniform protection with no detectable viremia. The vaccine induced B and T cell proliferation and, importantly, antigen-specific IgG production. Transcriptomic signatures confirm these findings and suggest innate immunity engendered by VSV-MARV may direct the development of protective humoral immunity.
Highlights
Marburg virus (MARV) is a member of the Filoviridae, a family of non-segmented, negative-stranded RNA viruses that cause severe hemorrhagic fever with case fatality rates (CFR) ranging from 23 to 90% in humans and 100% lethality in nonhuman primates (NHPs) following experimental infection [1]
Marburg hemorrhagic fever (MHF) is similar to the disease caused by Ebola virus (EBOV) and is characterized by fever, an excessive inflammatory response, coagulation abnormalities, and vesicular stomatitis virus (VSV)-MARV Protects From Lethal Challenge vascular hemorrhaging [1]
VSV-MARV expressing the MARV-Angola GP was used for this study; we generated this vector in order to update the vaccine to express the most recently circulating GP in Africa
Summary
Marburg virus (MARV) is a member of the Filoviridae, a family of non-segmented, negative-stranded RNA viruses that cause severe hemorrhagic fever with case fatality rates (CFR) ranging from 23 to 90% in humans and 100% lethality in nonhuman primates (NHPs) following experimental infection [1]. Since 1967, several outbreaks and sporadic cases have been reported in Angola, The Democratic Republic of Congo (DRC), Kenya, South Africa and Uganda, with the largest outbreaks occurring in 1998–2000 in the DRC (154 cases, 83% CFR) and in 2004–2005 in Angola [374 cases, 88% CFR [6]]; in addition, single human MARV cases were imported into the Netherlands and the USA [1]. Marburg hemorrhagic fever (MHF) is similar to the disease caused by Ebola virus (EBOV) and is characterized by fever, an excessive inflammatory response, coagulation abnormalities, and VSV-MARV Protects From Lethal Challenge vascular hemorrhaging [1]. Disseminated intravascular coagulation was noted at the late stages of disease as evidenced by increased levels of D-dimers and fibrin deposition in tissues, albeit with reduced severity compared to EBOV infection in NHPs [7]
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