Ebola Virus‐Like Particle–Based Vaccine Protects Nonhuman Primates against Lethal Ebola Virus Challenge

Warfield, Kelly L.; Swenson, Dana L.; Olinger, Gene G.; Kalina, Warren V.; Aman, M. Javad; Bavari, Sina

doi:10.1086/520583

Cited by 234 publications

(232 citation statements)

References 39 publications

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“…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%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

106

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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%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

106

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“…CD4 and CD8 IFN-γ responses to EBOV antigens including peptide pools (GP1-3 and NP) and recombinant proteins (rGP and rVP40) were assessed 2 wk after the last vaccination (study day 70) (Fig. 3D) (13,15). Stimulation of peripheral blood mononuclear cell (PBMCs) with six EBOV antigens produced mean twofold and sixfold increases in production of IFN-γ in CD4 and CD8 T cells compared with no stimulation (15).…”

Section: Resultsmentioning

confidence: 99%

“…Because they do not cause infection, VLP-based vaccines are particularly safe and several have been recently approved for human use (12). We tested a VLP vaccine based on the virulent Zaire species of EBOV that previously has been given to more than 80 captive macaques without serious health complications (13). In the present study, we did not challenge vaccinated chimpanzees with EBOV.…”

mentioning

confidence: 99%

Vaccinating captive chimpanzees to save wild chimpanzees

Warfield

Goetzmann

Biggins

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Although infectious disease is now recognized as a major threat to wild gorillas and chimpanzees, safety fears have stifled the use of a powerful disease control tool, vaccination. To illustrate that safety can be rigorously evaluated before vaccines are used on wild apes, we conducted what is, to our knowledge, the first conservation-oriented vaccine trial on captive chimpanzees. We tested an experimental virus-like particle (VLP) vaccine against Ebola virus, a leading killer of wild apes. Our trial illustrates both the ape conservation value that will be lost if efforts to end vaccine trials on captive chimpanzee are successful and the broader potential that noninfectious VLP vaccines have in other wildlife applications.

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“…Filovirus VLPs potently stimulated functional maturation and activation of dendritic cells in vitro, which is likely responsible for activation of both humoral and cellular immune responses. 13 Similar to the viral replicon, additional efforts in optimizing the formulation of a VLP-based vaccine may shed light on strategies to induce effective cross-protection. The final product may be a tri-component vaccine consisting of separate VLPs for Marburg virus, Ebola Virus Zaire and Ebola Virus Sudan, but could be flexible to incorporate emerging strains as well.…”

Section: Basic Researchmentioning

confidence: 99%