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Vaccine Detail

DNA and poxvirus priming-boosting SHIV vaccine
Vaccine Information
  • Vaccine Name: DNA and poxvirus priming-boosting SHIV vaccine
  • Target Pathogen: Human Immunodeficiency Virus
  • Target Disease: Acquired Immunodeficiency Syndrome (AIDS)
  • Vaccine Ontology ID: VO_0000825
  • Type: DNA vaccine
  • Antigen: SHIV89.6P env and SIVmac239 gag (Santra et al., 2004)
  • env gene engineering:
    • Type: DNA vaccine 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.
  • DNA vaccine plasmid:
    • DNA vaccine plasmid name:
    • DNA vaccine plasmid VO ID: VO_0000993
  • Preparation: The recombinant vaccinia viruses (rVac) expressing SHIV89.6P env and SIVmac239 gag were constructed by inserting these genes in the HindIII M region of TBC-Wy, Therion strain of vaccinia. rFPV viruses expressing these same genes were constructed by inserting the genes in the BamJHI region of POXVAC-TC (Schering-Plough) strain of FPV (Santra et al., 2004).
  • Description: An HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, but the characteristics of effective vaccine-induced CTL response remain unclear. The SHIV/rhesus monkey model has been used to in the course of assessing the relative immunogenicity of vaccine regimens that include a cytokine-augmented plasmid DNA prime and a boost with DNA or recombinant pox vectors. This study indicates that the steady-state memory, rather than the peak effector vaccine-elicited CTL responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine (Santra et al., 2004).
Host Response

Monkey Response

  • Host Strain: rhesus monkey (Macaca mulatta)
  • Vaccination Protocol: Nonrecombinant wildtype vaccinia virus was designated VV-WT, wild-type fowlpox virus was designated FPV-WT, and wild-type MVA was designated MVA-WT. These wild-type viruses were used as control vector immunogens (Santra et al., 2004). One group of monkeys were vaccinated by separate i.m. injections of HIV-1. Half the dose was delivered to each quadriceps muscle. Seven of the 28 monkeys were vaccinated by both i.d. and i.m. injections of rFPV expressing HIV-1 89.6P Env and the same virus expressing SIV mac239 Gag. Seven monkeys received rMVA-HIV-189.6P Env and rMVA-SIVmac239 Gag, and another seven monkeys received rVac-HIV-1 89.6P Env and rVac-SIVmac239 Gag administered both i.d. and i.m. Another 28 monkeys received sham plasmid DNA and empty pox vectors (Santra et al., 2004).
  • Persistence: Persistence levels were measured 2 weeks after challenge with results mentioned in Challenge Protocol section (Santra et al., 2004).
  • Immune Response: Recombinant vaccinia virus, MVA, and fowlpox were comparable in their immunogenicity. Magnitude of peak vaccine-elicited CTL responses in pox virus-boosted monkeys is substantially greater than that seen in monkeys immunized with plasmid DNA alone, but magnitudes of recombinant pox boosted CTL responses decayed rapidly and were comparable to those of the DNA-alone vaccinated monkeys by the time of viral challenge. Clinical protection seen in all groups of experimentally vaccinated monkeys is similar, indicating that steady-state memory, rather than peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine (Santra et al., 2004).
  • Challenge Protocol: Eighteen weeks after the final immunization, all animals were challenged with cell-free SHIV-89.6P i.v. (Santra et al., 2004).
  • Efficacy: Control monkeys developed tetramer-binding CD8 T lymphocyte responses that were maximal 2 weeks after viral challenge and no detectable p41A-specific CD8 T cells. In contrast, all four groups of vaccinated monkeys developed robust secondary p11C-specific CTL responses that were comparable in magnitude. Animals boosted with plasmid DNA had Gag p11C-specific CD8 T cell responses similar in magnitude to that seen in the recombinant pox virus-boosted animals. Magnitudes of the postchallenge IFN ELISPOT responses to both vaccine antigens were comparable in all four experimentally vaccinated groups of monkeys. Therefore, although the pre-challenge peak vaccine-elicited immune responses were greater in the groups of monkeys boosted with recombinant pox vectors, the pre-challenge plateau and post-challenge peak secondary responses were equivalent in magnitude in all four experimental groups of animals (Santra et al., 2004).
  • Host IFNG response
    • Description: There was a greater contraction of the vaccine-elicited IFN-γ-secreting T cell responses in the groups of monkeys boosted with recombinant pox vectors than in the group of animals boosted with plasmid DNA. Although the pre-challenge peak vaccine-elicited immune responses were greater in the groups of monkeys boosted with recombinant pox vectors, the pre-challenge plateau and post-challenge peak secondary responses were equivalent in magnitude in all four experimental groups of animals (Santra et al., 2004).
    • Detailed Gene Information: Click Here.
References
Santra et al., 2004: Santra S, Barouch DH, Korioth-Schmitz B, Lord CI, Krivulka GR, Yu F, Beddall MH, Gorgone DA, Lifton MA, Miura A, Philippon V, Manson K, Markham PD, Parrish J, Kuroda MJ, Schmitz JE, Gelman RS, Shiver JW, Montefiori DC, Panicali D, Letvin NL. Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses. Proceedings of the National Academy of Sciences of the United States of America. 2004 Jul 27; 101(30); 11088-93. [PubMed: 15258286].