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Vaccine Detail

Adenoviral vector Ad5 expressing SIV gag protein
Vaccine Information
  • Vaccine Name: Adenoviral vector Ad5 expressing SIV gag protein
  • Target Pathogen: Human Immunodeficiency Virus
  • Target Disease: Acquired Immunodeficiency Syndrome (AIDS)
  • Vaccine Ontology ID: VO_0000788
  • Type: Recombinant vector vaccine
  • Status: Research
  • Antigen: SIVmac239 gag protein (Shiver et al., 2002)
  • Gag protein from SIV-mnd 2 gene engineering:
    • Type: Recombinant vector construction
    • Description:
    • Detailed Gene Information: Click Here.
  • Preparation: The adenoviral vector was based on a serotype 5 adenovirus that is incompetent to replicate with deletion of the E1 and E3 viral genes, and was propagated subsequently in E1-expressing 293 cells. Recombinant adenovirus expressing the codon-optimized SIV gag gene was then prepared. The recombinant adenovirus (Ad5-SIVgag) was grown in large quantities by multiple rounds of amplification in 293 cells. The virus was purified by caesium chloride gradient centrifugation (Shiver et al., 2002).
  • Immunization Route: Intramuscular injection (i.m.)
Host Response

Monkey Response

  • Host Strain: rhesus monkey (Macaca mulatta)
  • Vaccination Protocol: In this study, 21 rhesus monkeys were divided into 6 groups, including an unimmunized control cohort. Each of the test vectors expressed the identical SIVmac239 gag gene that had been codon optimized for expression in mammalian cells. In the first study, the two viral vector vaccines were administered, followed by a booster dose; preparations of DNA plasmid vector vaccine were delivered thrice, followed by a booster (Shiver et al., 2002).
  • Immune Response: In general, all of the monkeys developed p11CM-specific cellular immune responses after the initial immunization series. The p11CM (residues 181–189) is an immunodominant SIV gag epitope that is presented by the Mamu-A*01 MHC protein and is capable of binding T-cell receptors in the model monkeys. Administration of the third dose of the Ad5 vector resulted in an additional increase of p11CM-specific CD8+ T cells at the time of virus challenge. After the booster inoculation, these animals exhibited peak levels of p11CM-specific CD8+ T cells (Shiver et al., 2002).
  • Challenge Protocol: At 12 weeks after the final immunization, all monkeys were challenged i.v. with the pathogenic HIV–SIV hybrid virus (SHIV) 89.6P16. The challenge of the control and immunized animals within the context of each of the two independent studies occurred concurrently (Shiver et al., 2002).
  • Efficacy: Each of the animals in both control groups exhibited acute CD4+ T-cell lymphopenia and peak viral loads of viral RNA copies at about 3 weeks after challenge. With the exception of one animal, all of the control monkeys experienced dramatic loss of CD4+ T cells. During the acute phase of the infection, most monkeys immunized with either the DNA or MVA vectors exhibit an acute CD4+ T-cell lymphopenia. By about 70 d after challenge, many of the immunized monkeys exhibit some evidence of a positive immunization benefit, as manifested by control of viremia and recovery of CD4+ T-cell counts. However, the animals immunized with Ad5 vector exhibited the most pronounced attenuation of the infection with a pathogenic HIV–SIV hybrid virus (SHIV) (Shiver et al., 2002).
References
Shiver et al., 2002: Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schleif WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature. 2002 Jan 17; 415(6869); 331-5. [PubMed: 11797011].