VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain

Marzi, Andrea; Robertson, Shelly J.; Haddock, Elaine; Feldmann, Friederike; Hanley, Patrick W.; Scott, Dana; Strong, James E.; Kobinger, Gary P.; Best, Sonja M.; Feldmann, Heinz

doi:10.1126/science.aab3920

Cited by 218 publications

(267 citation statements)

References 23 publications

(28 reference statements)

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“…Nearly all these vaccines use filovirus glycoprotein (GP) as the protective immunogen. These vaccines completely protected NHPs against lethal disease and are mostly replication-defective or replication-competent viral vectors, including alphavirus replicons 241,242 , human adenoviruses [243][244][245][246][247] , chimpanzee adenoviruses 248 , paramyxoviruses 249,250 , rabies viruses 251,252 and several different strategies with recombinant vesicular stomatitis viruses (rVSVs), including both the prototype rVSV vaccine [253][254][255][256][257] and a newer rVSV vaccine developed for enhanced safety (VesiculoVax) 258 . Virus-like particles [259][260][261] , a biologically contained EBOV lacking viral protein 30 (VP30) 262 , DNA 244 and several combinations of vaccines that include DNA, modified vaccinia Ankara (MVA) and various adenoviruses can also completely protect NHPs from lethal filovirus disease 244,248,263 .…”

Section: Box 2 | Vaccination To Prevent Filovirus Infectionmentioning

confidence: 99%

“…An important consideration for any filovirus vaccine is the ability to provide rapid protection, as outbreaks, epidemics and bioterrorist events do not allow time for a multiple-injection strategy. Several filovirus vaccines prevent infection in NHPs when used as single injections 232,233,247,253,254,257,258 . In particular, the rVSV filovirus vaccines are very potent in this regard and can completely protect NHPs against EBOV, even if administered as few as 7 days before high-dose EBOV (Makona strain) challenge 257 .…”

Section: Box 2 | Vaccination To Prevent Filovirus Infectionmentioning

confidence: 99%

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Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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Section: Box 2 | Vaccination To Prevent Filovirus Infectionmentioning

confidence: 99%

Section: Box 2 | Vaccination To Prevent Filovirus Infectionmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

Self Cite

106

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“…20 Based on the absence of antigen-specific antibody responses in the animals vaccinated 3 days before challenge, protection in this group was most likely based on activation of the innate immune response by VSV-EBOV vaccination, providing short-term protection for the duration necessary to develop an EBOV-specific adaptive immune response. This study clearly demonstrated the feasibility of using the VSV-EBOV vaccine in outbreak situations where a short time to protection is essential to aid in reducing transmission of the virus.…”

Section: Introductionmentioning

confidence: 99%

“…10 , 13 Importantly, it was shown that vaccination of cynomolgus macaques with a VSV-EBOV vaccine expressing the GP from the EBOV-Kikwit strain, isolated during the 1995 EBOV outbreak in Kikwit, Democratic Republic of the Congo, 21 that was subsequently used in clinical trials resulted in complete protection from lethal challenge with the EBOV-Makona strain isolated during the West African EBOV epidemic. 20 Thus, the currently available VSV-EBOV vaccine will likely be protective in future EBOV outbreaks.…”

Section: Introductionmentioning

confidence: 99%

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

Suder

Furuyama

Feldmann

et al. 2018

Human Vaccines & Immunotherapeutics

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111

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The devastating Ebola virus (EBOV) epidemic in West Africa in 2013–2016 accelerated the progress of several vaccines and antivirals through clinical trials, including the replication-competent vesicular stomatitis virus-based vaccine expressing the EBOV glycoprotein (VSV-EBOV). Extensive preclinical testing in animal models demonstrated the prophylactic and post-exposure efficacy of this vaccine, identified the mechanism of protection, and suggested it was safe for human use. Based on these data, VSV-EBOV was extensively tested in phase 1–3 clinical trials in North America, Europe and Africa. Although some side effects of vaccination were observed, these clinical trials showed that the VSV-EBOV was safe and immunogenic in humans. Moreover, the data supported the use of VSV-EBOV as an emergency vaccine in individuals at risk for Ebola virus disease. In this review, we summarize the results of the extensive preclinical and clinical testing of the VSV-EBOV vaccine.

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“…This also seems supported by initial infection studies in macaques, which did not result in increased virulence of the West African EBOV Makona strain (8), as well as by the first experiments in humanized mice, where infection with a wild-type EBOV Makona isolate resulted in a longer mean-timeto-death than infection with the prototype EBOV Mayinga strain from 1976 (9). Similarly, a vaccine that was developed against the EBOV Kikwit strain from 1995 remains protective against the West African EBOV Makona strain from 20 years later in the macaque model (10) and has shown promising results in a human ring vaccination trial (11). Also, a first experimental study addressing sequence changes occurring early in the epidemic did not reveal evidence for altered virus biology between different EBOV Makona variants or between EBOV Makona and EBOV Mayinga (12), and comparative studies of virus entry also revealed no differences between EBOV Makona and EBOV Mayinga (13).…”

mentioning

confidence: 99%