Effective Post-Exposure Treatment of Ebola Infection

Abstract

Ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in Central Africa and a potential for use as a biological weapon. There is no vaccine or treatment licensed for human use. In the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. In this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein completely protected rodents and nonhuman primates from lethal Ebola challenge. In contrast, progress in developing therapeutic interventions against Ebola virus infections has been much slower and there is clearly an urgent need to develop effective post-exposure strategies to respond to future outbreaks and acts of bioterrorism, as well as to treat laboratory exposures. Here we tested the efficacy of the vesicular stomatitis virus-based Ebola vaccine vector in post-exposure treatment in three relevant animal models. In the guinea pig and mouse models it was possible to protect 50% and 100% of the animals, respectively, following treatment as late as 24 h after lethal challenge. More important, four out of eight rhesus macaques were protected if treated 20 to 30 min following an otherwise uniformly lethal infection. Currently, this approach provides the most effective post-exposure treatment strategy for Ebola infections and is particularly suited for use in accidentally exposed individuals and in the control of secondary transmission during naturally occurring outbreaks or deliberate release.

How Ebola and Marburg viruses battle the immune system

“…Mechanistically, additional immunological and virological puzzles have been exposed by recent demonstrations of protective effects of vaccinating rodents or primates with replication-competent vaccines shortly before or shortly after infection with MARV 82 or EBOV 83 . Surmising that protective mechanisms in this exceptional circumstance could be 'multifactorial' , Feldmann et al proposed as possible explanations not only antibodies and T cells, but also NK cells, innate immune responses and viral interference (attenuated-vaccine virus out-competing virulent filoviruses at the cellular level) 83 .…”

The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

“…Mice were fully protected from death and disease when vaccinated as shortly as 24 hours before challenge with MA-EBOV and exhibited only mild disease when treated up to 24 hours post challenge. 17 In guinea pigs, partial protection from lethal challenge with guinea pig-adapted EBOV (GPA-EBOV) was observed when animals were vaccinated 24 hours prior to challenge, 1 hour post challenge, or 24 hours post challenge (66%, 83%, and 50% survival, respectively). 17 Hamsters vaccinated up to 3 days prior to challenge with MA-EBOV were fully protected and generated high antibody titers without displaying clinical signs of disease.…”

“…17 In guinea pigs, partial protection from lethal challenge with guinea pig-adapted EBOV (GPA-EBOV) was observed when animals were vaccinated 24 hours prior to challenge, 1 hour post challenge, or 24 hours post challenge (66%, 83%, and 50% survival, respectively). 17 Hamsters vaccinated up to 3 days prior to challenge with MA-EBOV were fully protected and generated high antibody titers without displaying clinical signs of disease. In a post-exposure study, all hamsters in the groups treated immediately or 24 hours after challenge survived, while all hamsters treated 48 hours after challenge succumbed to MA-EBOV infection.…”

“…17 Control animals treated with the VSV-Marburg virus (VSV-MARV) vaccine were not protected from lethal disease. 17 Post-exposure efficacy of the VSV-EBOV vaccine against EBOV-Makona, the EBOV strain causing the 2013–2016 West African epidemic, was shown in rhesus macaques, where 50% of animals survived lethal challenge when treated with VSV-EBOV at 1 and/or 24 hours post challenge.…”

“…17 Control animals treated with the VSV-Marburg virus (VSV-MARV) vaccine were not protected from lethal disease. 17 Post-exposure efficacy of the VSV-EBOV vaccine against EBOV-Makona, the EBOV strain causing the 2013–2016 West African epidemic, was shown in rhesus macaques, where 50% of animals survived lethal challenge when treated with VSV-EBOV at 1 and/or 24 hours post challenge. In contrast to the post-exposure study, partial survival was also observed in the group of animals treated twice with a control vaccine, the VSV-MARV vaccine, and challenged with EBOV-Makona, again indicating that the mechanism of a short time to protection was most likely based on a non-specific induction of the innate immune system by VSV rather than an antigen-specific response.…”