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Vaccine Comparison

Ebola virus recombinant adenovirus vector vaccine ADV−GP/NP GP and NP
Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0004072
  • Type: Recombinant vector vaccine
  • Status: Research
  • GP from Zaire ebolavirus gene engineering:
    • Type: DNA vaccine construction
    • Description: Vector adenoviral (ADV) expressed Ebola glycoprotein (GP) (Sullivan et al., 2003b).
    • Detailed Gene Information: Click Here.
  • NP from Zaire Ebola virus gene engineering:
    • Type: Recombinant vector construction
    • Description: Vector adenoviral (ADV) expressed Ebola nucleoprotein (NP) (Sullivan et al., 2003b).
    • Detailed Gene Information: Click Here.
  • Preparation: To make ADV-GP, the BamHI/EcoRI fragment of GP(Z) was digested from PGEM-3Zf(-)-GP, treated with Klenow, and inserted into HindIII/XbaI/Kle/CIP-treated pRc/CMV plasmid. The resulting plasmid was digested by NruI/DraIII and treated with Klenow. The NruI/DraIII/Kle fragment containing the CMV enhancer, GP(Z) DNA and bovine growth hormone polyadenylation signal was inserted into the BgIII site of the adenoviral shuttle plasmid pAdBgIII26. The adenovirus, a first generation dl 309-based Ad5 vector, contained a deletion in E1 to render the vector replication defective and a partial deletion/substitution in E3, which disrupts the coding sequences for the E3 proteins with a relative molecular mass of 14,700, 14,500 and 10,400, respectively (Sullivan et al., 2000).
  • Virulence:
  • Description: ADV−GP consists of an adenoviral (ADV) vector encoding the Ebola glycoprotein (GP) (Sullivan et al., 2003).
  • Vaccine Ontology ID: VO_0004073
  • Type: VEEV Replicon
  • Preparation: The Ebola NP and GP genes from the Mayinga strain of Ebola virus were derived from pSP64- and pGEM3Zf(-)-based plasmids. The BamHI±EcoRI (2.3 kb) and BamHI±KpnI (2.4 kb) fragments containing the NP and GP genes, respectively, were subcloned into a shuttle vector digested with BamHI and EcoRI within a polylinker sequence flanked by ClaI sites. For cloning of the GP gene, overhanging ends produced by KpnI (in the GP fragment) and EcoRI (in the shuttle vector) were made blunt by incubation with T4 DNA polymerase. From the shuttle vector, NP or GP genes were transferred as ClaI-fragments into the ClaI site of the replicon clone, resulting in plasmids encoding the NP or GP gene in place of the VEE structural protein genes (Pushko et al., 2000).
  • Virulence:
  • Description: This immunogen is composed of RNA replicon particles derived from an attenuated strain of Venezuelan equine encephalitis virus (VEEV) expressing EBOV glycoprotein and nucleoprotein (Geisbert et al., 2002).
Host Response Host Response

Monkey Response

  • Host Strain: Cynomolgus macaque
  • Vaccination Protocol: Cynomolgus macaques were immunized with ADV−GP and ADV−NP, followed by boosting 9 weeks later (Sullivan et al., 2003).
  • Persistence: None noted
  • Side Effects: None noted
  • Challenge Protocol: One week after the boost, animals were challenged with either a low or high dose of a 1995 isolate of Ebola virus Zaire.
  • Efficacy: In the saline-injected control animals these doses were uniformly fatal 6−12 days afterwards. In contrast, the ADV−GP/NP immunized monkeys were completely protected. Analysis of the cell-mediated and humoral immune responses revealed significant increases in the CD8+ T-cell response to Ebola antigens by intracellular cytokine staining for interferon (IFN)-, seen before exposure to virus, in contrast to control animals where no response was seen. Similarly, antibody titres to the virus were stimulated in vaccinated animals, which minimally increased after the viral challenge (Sullivan et al., 2003).

Monkey Response

  • Host Strain: Cynomolgus macaques
  • Vaccination Protocol: Groups of three cynomolgus macaques were vaccinated with VRP that expressed EBOV GP, EBOV NP, a mixture of EBOV GP and EBOV NP, or a control antigen (influenza hemagglutinin) that has no effect on EBOV immunity. Animals were vaccinated by subcutaneous injection of 107 focus-forming units of VRP in a total of 0.5 mL at one site. Vaccinations were repeated 28 days after the first injection and 28 days after the second (Geisbert et al., 2002).
  • Persistence: None noted
  • Side Effects: None noted
  • Efficacy: These results indicate that rodent models of EBOV hemorrhagic fever do not consistently predict efficacy of candidate vaccines in nonhuman primates, perhaps because the disease course in rodents differs from that reported in human and nonhuman primates (Geisbert et al., 2002).
  • Description: All animals, including the four untreated macaques, were challenged with 1,000 PFU of EBOV 49 days after the third vaccine dose. At postchallenge day 3, all animals became ill; two animals from each vaccination group (i.e., GP, NP, GP + NP, influenza HA) died on day 6, and the remaining animals died on day 7 (Geisbert et al., 2002).
References References
Sullivan et al., 2000: Sullivan NJ, Sanchez A, Rollin PE, Yang ZY, Nabel GJ. Development of a preventive vaccine for Ebola virus infection in primates. Nature. 2000 Nov 30; 408(6812); 605-9. [PubMed: 11117750].
Sullivan et al., 2003b: Sullivan NJ, Geisbert TW, Geisbert JB, Xu L, Yang ZY, Roederer M, Koup RA, Jahrling PB, Nabel GJ. Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature. 2003 Aug 7; 424(6949); 681-4. [PubMed: 12904795].
Geisbert et al., 2002: Geisbert TW, Pushko P, Anderson K, Smith J, Davis KJ, Jahrling PB. Evaluation in nonhuman primates of vaccines against Ebola virus. Emerging infectious diseases. 2002 May; 8(5); 503-7. [PubMed: 11996686].
Pushko et al., 2000: Pushko P, Bray M, Ludwig GV, Parker M, Schmaljohn A, Sanchez A, Jahrling PB, Smith JF. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus. Vaccine. 2000 Aug 15; 19(1); 142-53. [PubMed: 10924796].