Abstract
The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.
Highlights
The order Mononegavirales comprises the non-segmented, negative sense, single-stranded RNA viruses in the family Filoviridae along with the families Rhabdoviridae, Paramyxoviridae, and Bornaviridae
Ebola and Marburg viruses are categorized as Category A priority pathogens by several US Government agencies as a result of their high mortality rates and potential for use as agents of bioterrorism
We used a conventional neurovirulence test to evaluate the safety of our rVSVbased Zaire ebolavirus and Lake Victoria marburgvirus GP vaccines in cynomolgus macaques
Summary
The order Mononegavirales comprises the non-segmented, negative sense, single-stranded RNA viruses in the family Filoviridae along with the families Rhabdoviridae, Paramyxoviridae, and Bornaviridae. The family Filoviridae contains two genera, Ebolavirus (EBOV) and Marburgvirus (MARV) [1,2]. The Ebolavirus genus has accounted for at least 22 outbreaks dating back to 1976 with of these occurring within the last 20 years [4]. The Marburgvirus genus has one species, Lake Victoria marburgvirus, that has been responsible for at least nine outbreaks since 1967 with five of these occurring in the last decade [4]. The increased frequency of EBOV and MARV outbreaks along with the fact that these viruses are potential agents of bioterrorism has increased public health concern regarding filoviruses. There are no licensed vaccines or postexposure treatments available for human use; there are at least six different vaccine candidates that have shown the potential to protect nonhuman primates (NHP) from lethal EBOV and/or MARV infection [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]
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