Vaccine To Confer to Nonhuman Primates Complete Protection against Multistrain Ebola and Marburg Virus Infections

Swenson, Dana L.; Wang, Danher; Luo, Min; Warfield, Kelly L.; Woraratanadharm, Jan; Holman, David H.; Dong, John Y.; Pratt, William D.

doi:10.1128/cvi.00431-07

Cited by 113 publications

(88 citation statements)

References 42 publications

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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%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

107

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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

107

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“…The adenovirus-based vector, a replication-incompetent vector, is based on a human pathogen (adenovirus type 5), raising concerns of preexisting immunity to the vector. In addition, a large dose of this virus (10 10 particles) is needed to confer protection in NHPs (29,32,35). A vaccine based on the VSV vector protects NHPs at reasonable doses; however, this vector is replication competent and safety is, therefore, a concern, particularly the potential for infection of the human central nervous system (24).…”

Section: Discussionmentioning

confidence: 99%

Replication-Deficient Ebolavirus as a Vaccine Candidate

Halfmann

Ebihara

Marzi

et al. 2009

J Virol

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Ebolavirus causes severe hemorrhagic fever, with case fatality rates as high as 90%. Currently, no licensed vaccine is available against Ebolavirus. We previously generated a replication-deficient, biologically contained Ebolavirus, Ebola⌬VP30, which lacks the essential VP30 gene, grows only in cells stably expressing this gene product, and is genetically stable. Here, we evaluated the vaccine potential of Ebola⌬VP30. First, we demonstrated its safety in STAT-1-knockout mice, a susceptible animal model for Ebolavirus infection. We then tested its protective efficacy in two animal models, mice and guinea pigs. Mice immunized twice with Ebola⌬VP30 were protected from a lethal infection of mouse-adapted Ebolavirus. Virus titers in the serum of vaccinated mice were significantly lower than those in nonvaccinated mice. Protection of mice immunized with Ebola⌬VP30 was associated with a high antibody response to the Ebolavirus glycoprotein and the generation of an Ebolavirus NP-specific CD8 ؉ T-cell response. Guinea pigs immunized twice with Ebola⌬VP30 were also protected from a lethal infection of guinea pig-adapted Ebolavirus. Our study demonstrates the potential of the Ebola⌬VP30 virus as a new vaccine platform.

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“…One platform, recombinant vesicular stomatitis virus, has demonstrated prophylactic and postexposure protection in nonhuman primates. Many of these candidates have shown outstanding technical utility-especially the viral vectors (11)(12)(13). However, although highly active in controlled clinical settings, these candidate vaccines pose challenges for incorporation into a national biodefense stockpile, in which longterm vaccine stability with minimal cold chain requirements for storage and distribution are key factors in a successful program.…”

mentioning

confidence: 99%

A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge

Phoolcharoen

Dye

Kilbourne

et al. 2011

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

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Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola virus (EBOV). The possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. We have evaluated the immunogenicity and efficacy of an EBOV vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resulting in the production of Ebola immune complexes (EICs). Although antigen–antibody immune complexes are known to be efficiently processed and presented to immune effector cells, we found that codelivery of the EIC with Toll-like receptor agonists elicited a more robust antibody response in mice than did EIC alone. Among the compounds tested, polyinosinic:polycytidylic acid (PIC, a Toll-like receptor 3 agonist) was highly effective as an adjuvant agent. After vaccinating mice with EIC plus PIC, 80% of the animals were protected against a lethal challenge with live EBOV (30,000 LD 50 of mouse adapted virus). Surviving animals showed a mixed Th1/Th2 response to the antigen, suggesting this may be important for protection. Survival after vaccination with EIC plus PIC was statistically equivalent to that achieved with an alternative viral vector vaccine candidate reported in the literature. Because nonreplicating subunit vaccines offer the possibility of formulation for cost-effective, long-term storage in biothreat reduction repositories, EIC is an attractive option for public health defense measures.

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Vaccine To Confer to Nonhuman Primates Complete Protection against Multistrain Ebola and Marburg Virus Infections

Cited by 113 publications

References 42 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Replication-Deficient Ebolavirus as a Vaccine Candidate

A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge

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