Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus

Pushko, Peter; Bray, Mike; Ludwig, George V.; Parker, Michael D.; Schmaljohn, Alan L.; Sanchez, Anthony; Jahrling, Peter B.; Smith, Jonathan

doi:10.1016/s0264-410x(00)00113-4

Cited by 189 publications

(156 citation statements)

References 40 publications

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“…2). Recombinant replicons expressing the full-length GP gene and packaged into Venezuelan equine encephalitis virus (VEE) replicon particles (GP-VRP) (15) and PBS solution were used as a positive and negative vaccine control, respectively.…”

Section: Pic Codelivered With Eic Induced a Robust Anti-ebov Igg Respmentioning

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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Section: Pic Codelivered With Eic Induced a Robust Anti-ebov Igg Respmentioning

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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“…However, in guinea pigs challenged with MARV, only viral glycoprotein, nucleoprotein and VP35 afforded some measure of protection when used as vaccines in a replicon-based vector system 4 . In guinea pigs vaccinated and then challenged with ZEBOV, viral glycoprotein was a superior protective antigen, with nucleoprotein providing no 62 or equivocal 63 protection. In the case of non-human primates that had been vaccinated and then challenged with either MARV or ZEBOV, viral glycoprotein has proved to be necessary and sufficient as a vaccine component.…”

Section: Anergymentioning

confidence: 99%

How Ebola and Marburg viruses battle the immune system

2007

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PantropicTending towards the capacity to infect a wide range of cells and organs. CoagulopathyRefers to a group of conditions of the blood-clotting system in which bleeding is prolonged and excessive. Cell tropismA virus's affinity for or tendency towards preferential infection of certain cells. How Ebola and Marburg viruses battle the immune systemMansour Mohamadzadeh* ‡ , Lieping Chen ‡ , and Alan L. Schmaljohn* Abstract | The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. Filoviruses have provided thereby a new lens through which to examine the immune system itself. R E V I E W S Report Documentation PageForm Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.

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“…The guinea pigs that survived challenge were found to be viremic on day 7 after challenge. In a similar study, strain 13 guinea pigs inoculated with VEEV-replicons expressing GP produced about the same level of antibodies as the strain 2 guinea pigs but were completely protected from a guinea pig-adapted EBOV challenge [80,82]. No viremia was detected in these animals 7 days after challenge.…”

Section: Veev-vectored Ebola Hemorrhagic Fever and Marburg Virus Vaccmentioning

confidence: 78%

“…Strain 2 guinea pigs inoculated with replicons expressing either EBOV GP or NP produced antibodies against EBOV but were either partially protected or not protected from a guinea pig-adapted EBOV challenge, respectively [80,81]. The guinea pigs that survived challenge were found to be viremic on day 7 after challenge.…”

Section: Veev-vectored Ebola Hemorrhagic Fever and Marburg Virus Vaccmentioning

confidence: 99%

Viral vectors for use in the development of biodefense vaccines

Lee

Hadjipanayis

Parker

2005

Advanced Drug Delivery Reviews

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Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus

Cited by 189 publications

References 40 publications

A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge

A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge

How Ebola and Marburg viruses battle the immune system

Viral vectors for use in the development of biodefense vaccines

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