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Vaccine Detail

DNA vaccine expressing multiple HIV epitopes
Vaccine Information
  • Vaccine Name: DNA vaccine expressing multiple HIV epitopes
  • Target Pathogen: Human Immunodeficiency Virus
  • Target Disease: Acquired Immunodeficiency Syndrome (AIDS)
  • Vaccine Ontology ID: VO_0000817
  • Type: DNA vaccine
  • Antigen: The antigens are named MultiHIV-A (based on the subtype A consensus sequence), MultiHIV-B (subtype B consensus sequence), MultiHIV-C, and MultiHIV-FGH (based on ancestral sequence for subtypes F, G, and H). The MultiHIV DNAs encode polypeptides consisting of a fusion of the full-length regulatory proteins Rev, Nef and Tat as well structural proteins p17 and p24 (Malm et al., 2005).
  • rev from HIV 1 gene engineering:
    • Type: DNA vaccine construction
    • Description:
    • Detailed Gene Information: Click Here.
  • Nef gene engineering:
    • Type: DNA vaccine construction
    • Description:
    • Detailed Gene Information: Click Here.
  • Tat gene engineering:
    • Type: DNA vaccine construction
    • Description:
    • Detailed Gene Information: Click Here.
  • Gag from HIV 1 gene engineering:
    • Type: DNA vaccine construction
    • Description:
    • Detailed Gene Information: Click Here.
  • env gene engineering:
    • Type: DNA vaccine construction
    • Description:
    • Detailed Gene Information: Click Here.
  • pol gene engineering:
    • Type: DNA vaccine construction
    • Description:
    • Detailed Gene Information: Click Here.
  • DNA vaccine plasmid: Auxo-GTU DNA vaccine plasmid
  • Preparation: A vaccine platform was constructed with an HIV-1 subtype B DNA immunogen expressing full-length consensus sequences from HIV-1 rev, nef, tat, and gag with additional cellular epitope clusters from the env and pol regions. Furthermore, this platform has been extended to three additional plasmids expressing the same immunogens but originating from subtypes A or C consensus or FGH ancestral sequences (Malm et al., 2005).
  • Description: A significant limitation for HIV vaccine development is that there are no small animals in which actual productive HIV-1 infection can be established. DNA immunization with candidate vaccines comprising multiple genes of clades A, B, C, F, G, and H create strong cellular responses in BALB/c mice, especially after gene gun immunization (Malm et al., 2005).
Host Response

Mouse Response

  • Host Strain: C57BL/6, BALB/c
  • Vaccination Protocol: C57BL/6 mice were divided into groups g.g. immunized or i.m. inoculated. Mice were bled 2 weeks after the last immunization, and individual blood and spleen samples were collected post-challenge and used fresh in ELISPOT assays (Malm et al., 2005).
    BALB/c were immunized by MultiHIV/MultiClade DNA. Initially the immune response was evaluated after 3 immunizations by g.g. Equal amounts of clade A, B, C, and FGH MultiHIV plasmids were mixed together and coated onto the gold particles to construct the subtype cocktail MultiHIV DNA immunogen (MultiHIVmix). Mice were sacrificed 10 days after the last immunization and individual spleens were collected and the cells preserved at –70°C until used. In a second set of experiments a short-term immunization schedule was used to address three different administration routes; g.g., i.m., and i.d. Mice were immunized 3 times with MultiHIVmix DNA (Malm et al., 2005).
  • Immune Response: Though the immune response detected was quite low, the majority of g.g. immunized animals responded with specific IFN production. Interestingly, the gag specific response in the same gene gun immunized animals was weaker than the envelope responses and also drastically weaker than the responses seen before the experimental challenge (Malm et al., 2005). The CTL response, following i.d. injection, was detected five weeks after the first immunization and persisted up to 12 weeks later. In contrast, i.m. immunization induced detectable IFNy only at week 17 (Malm et al., 2005).
  • Side Effects: no side effects occurred (Malm et al., 2005)
  • Challenge Protocol: C57BL/6 mice transgenic for HLA-A201 were given an experimental challenge after a short-term immunization schedule. Amphotropic murine leukemia virus was used to prepare pseudovirus with HIV-1 isolate. Challenged animals were given i.p. injections of sHIV-1/MuLV infected cells (Malm et al., 2005).
  • Efficacy: The vaccine-induced immunity has in vivo efficacy. Here a mouse model showed that the HIV-1 GTU-MultiHIVmix vaccine induces virus-specific CD8 T cellular immunity and protects against experimental HIV-1 challenge (Malm et al., 2005).
  • Description: The cocktail of MultiHIV protected 19/24 animals against an experimental HIV-1 challenge. This experiment also demonstrates cross-clade protection, as the subtypes A and B viruses used for challenge were derived from different subtypes than the sequences found in the clade A or B specific MultiHIV constructs. Furthermore, it demonstrates that consensus approach used in Multi-HIVmix vaccine is functional and causes protection against naturally occurring isolates. Gene gun immunization was superior to intramuscular immunization in terms of both the T cell immunity induced, as well as higher frequency of protection. Data generated in this work support the hypothesis that DNA representing several HIV-1 subtypes and several genes are immunogenic and protective (Malm et al., 2005).
  • Host Ifng (Interferon gamma) response
    • Description: IFN-gamma levels in mice immunized by gene gun or intramuscular delivery with HIV-1 subtype B DNA immunogen showed strong up regulation in response to an H-2d restricted gag peptide (AMQMLKETI) and even stronger up-regulation in response to an env epitope (RGPGRAFVTI) (Malm et al., 2005).
    • Detailed Gene Information: Click Here.
References
Malm et al., 2005: Malm M, Rollman E, Ustav M, Hinkula J, Krohn K, Wahren B, Blazevic V. Cross-clade protection induced by human immunodeficiency virus-1 DNA immunogens expressing consensus sequences of multiple genes and epitopes from subtypes A, B, C, and FGH. Viral immunology. 2005; 18(4); 678-88. [PubMed: 16359234].