Viral-vectored vaccines to control pathogenic filoviruses

For more than 35 years the filoviruses, Marburg virus and Ebola virus, have caused sporadic outbreaks of hemorrhagic fever that result in severe and often fatal disease in humans and nonhuman primates. Pathogenic Marburg and Ebola viruses are endemic in resource-poor regions in Central Africa and are also of concern as they have the potential for deliberate misuse. Although no vaccines or antiviral drugs for filoviruses are currently available for human use, remarkable progress has been made in developing candidate preventive vaccines against Marburg and Ebola viruses in nonhuman primate models. Most of these vaccines are based on viral vectors including recombinant adenoviruses, alphaviruses, paramyxoviruses, and rhabdoviruses. Because of the remote geographic locations of most filovirus outbreaks, a single-injection vaccine is an important goal in vaccine development. Among the prospective viral-vectored vaccines that have demonstrated efficacy in nonhuman primate models of filoviral hemorrhagic fever, two candidates, one based on a replication-defective adenovirus serotype 5 and the other on a recombinant vesicular stomatitis virus (rVSV), were shown to confer complete protection to nonhuman primates when administered as a single injection. Notably, the rVSV-based vaccines have also shown utility when used as postexposure treatments for filovirus infections.