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Vaccine Detail

VRP expressing VP35
Vaccine Information
  • Vaccine Name: VRP expressing VP35
  • Target Pathogen: Ebola virus
  • Target Disease: Ebola hemorrhagic fever
  • Vaccine Ontology ID: VO_0000783
  • Type: Recombinant vector vaccine
  • VP35 from Zaire ebolavirus gene engineering:
    • Type: Protein
    • Description:
    • Detailed Gene Information: Click Here.
  • Preparation: Replicon RNAs were packaged into particles. Briefly, capped replicon RNAs were produced in vitro by T7 runoff transcription of NotI-digested plasmid templates using the RiboMAX T7 RNA polymerase kit. BHK cells were cotransfected with the replicon RNAs and two RNAs expressing the VEE virus structural proteins. The cell culture supernatants were harvested approximately 30 h after transfection and the replicon particles were concentrated and partially purified by centrifugation through a 20% sucrose cushion. Packaged VRPs were suspended in phosphatebuffered saline and titers were determined as immunofluorescent foci after infection of Vero cells as described using either EBOV-immune rabbit serum or mouse monoclonal antibodies to VP24 (Z-AC01-BG11-01), VP35 (M-HC01-AF11), or VP40 (M-HD06-AD10) (Wilson et al., 2001).
  • Virulence:
  • Description: VP35 is an Ebola virus protein. It associates with the genomic RNA in a ribonucleoprotein complex. It is essential for replication and encapsidation of the EBOV genome. The VP35 protein has also recently been shown to be essential for the recovery of infectious EBOV-Z from cloned cDNAs. In addition to being an essential component of the replication complex, VP35 was also recently implicated as an interferon antagonist. VP35 may therefore facilitate viral replication in infected cells by blocking the induction of antiviral immune responses normally induced by the production of interferon (Wilson et al., 2001).
Host Response

Mouse Response

  • Host Strain: BALB/c and C57BL/6
  • Vaccination Protocol: Groups of 10 BALB/c or C57BL/6 mice per experiment were subcutaneously injected at the base of the neck with 2(10^6) focus-forming units of VRPs encoding the EBOV-Z genes, or with a control replicon encoding the Lassa N gene. Booster immunizations were administered at 1-month intervals (Wilson et al., 2001).
  • Persistence: None noted
  • Side Effects: None noted
  • Efficacy: The VP35 protein was not efficacious in the BALB/c mouse model, as only 20 and 26% of the mice were protected from lethal challenge after either two or three doses, respectively. The mean day of death of the VP-vaccinated mice that succumbed to the EBOV challenge was within 1 day of the control Lassa N-vaccinated mice. C57BL/6 mice were protected from lethal EBOV challenge after vaccination with the EBOV-Z VP35 protein, with 70% of the mice protected after three inoculations. When the viral titers were measured 5 days after challenge, vaccination with VRPs encoding the EBOV-Z VP35 protein reduced the viral load by at least 4 log10 compared to control mice. Most of the mice had detectable EBOV-Z-specific serum antibodies after vaccination with VRPs encoding the EBOV-Z VP protein (Wilson et al., 2001). These results indicate that the VP35 protein may be an important component of a vaccine designed to protect humans from Ebola hemorrhagic fever (Wilson et al., 2001).
References
Wilson et al., 2001: Wilson JA, Bray M, Bakken R, Hart MK. Vaccine potential of Ebola virus VP24, VP30, VP35, and VP40 proteins. Virology. 2001 Aug 1; 286(2); 384-90. [PubMed: 11485406].