• Vaccine Name: HIV DNA and adenoviral vector Ad5 expressing SIV gag protein
• Target Pathogen: Human Immunodeficiency Virus
• Target Disease: Acquired Immunodeficiency Syndrome (AIDS)
• Vaccine Ontology ID: VO_0000786
• Type: DNA 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.
• Gag protein from SIV-mnd 2 gene engineering:
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • Adjuvant name:
  • VO adjuvant ID: VO_0001318
• DNA vaccine plasmid:
  • DNA vaccine plasmid name:
  • DNA vaccine plasmid VO ID: VO_0000993
• Preparation: The V1R DNA vector expressed the identical SIVmac239 gag gene that had been codon optimized for expression in mammalian cells (Shiver et al., 2002). The plasmid DNA vector was formulated in a solution containing a nonionic blocked copolymer adjuvant (CRL1005) (Shiver et al., 2002).
  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.)
• Virulence: No virulence has been reported associated with this vaccine (Shiver et al., 2002).
• Description: Immunization and viral challenge studies were conducted in rhesus macaques (Macaca mulatta). Each of the test vectors expressed the identical SIVmac239 gag gene that had been codon optimized for expression in mammalian cells. The plasmid DNA vector was formulated in either PBS solution, a solution containing adjuvant, or a solution containing MPL/alum. All immunized animals were genotyped for the MHC class I Mamu-A*01 allele, allowing analysis of the responses of T cells (CD8+) to the test vaccines (Shiver et al., 2002).

Monkey Response

• Host Strain: rhesus monkey (Macaca mulatta)
• Vaccination Protocol: This study used 14 monkeys, 3 each in the immunized groups and 8 in the unimmunized control group. Each of the test vectors expressed the identical SIVmac239 gag gene that had been codon optimized for expression in mammalian cells. The DNA vector priming inoculations were administered, followed by viral vector boost inoculations (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).
• Side Effects: None of the vaccinated monkeys have yet exhibited any signs of immunodeficiency or suffered any consistent weight loss (Shiver et al., 2002).
• Challenge Protocol: At 6 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. 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 or with the DNA/CRL1005–MVA vector prime–boost combination 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).
• Host IFNG response
  • Description: Levels of interferon-gamma in monkeys stimulated intramuscularly with either the p11CM peptide or a pool of peptides derived from SIV gag were significantly upregulated and correlated well with the tetramer-staining results after the final boost. Intracellular IFN-[gamma]-staining assays confirmed that these responses were primarily mediated by CD8+ T cells (Shiver et al., 2002).
  • Detailed Gene Information: Click Here.