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Vaccine Detail

Melanoma DNA vaccine pCR3.1-VS-HSP65-TP-GRP6-M2 encoding 6 tandem repeats of GRP
Vaccine Information
  • Vaccine Name: Melanoma DNA vaccine pCR3.1-VS-HSP65-TP-GRP6-M2 encoding 6 tandem repeats of GRP
  • Target Pathogen: Cancer
  • Target Disease: Cancer
  • Vaccine Ontology ID: VO_0004433
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • GRP gene engineering:
    • Type: DNA vaccine construction
    • Description: This vaccine encoded six tandem repeats of a fragment of GRP from amino acids 18 to 27 (GRP6) flanked by helper T-cell epitopes for increased immunogenicity, including HSP65, a tetanus toxoid fragment from amino acids 830 to 844 (T), pan-HLA-DR-binding epitope (PADRE) (P), and two repeats of a mycobacterial HSP70 fragment from amino acids 407 to 426 (M) (Fang et al., 2009).
    • Detailed Gene Information: Click Here.
  • DNA vaccine plasmid:
    • DNA vaccine plasmid name:
    • DNA vaccine plasmid VO ID: VO_0000234
  • Immunization Route: Intramuscular injection (i.m.)
Host Response

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: B16-F10 cells injected subcutaneously formed large solid tumors in nonimmunized mice (saline) or in mice injected with a non-GRP-containing plasmid (pCR3.1-VS-HSP65-TP-M2). The tumor sizes decreased progressively in mice immunized with the anti-GRP vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2). B16-F10 tumor cells were implanted intradermally at two sites in the abdominal region. It took approximately 7 days for the cells to form ∼4-mm intradermal tumors in the two control groups; however, the growth of intradermal tumors in pCR3.1-VS-HSP65-TP-GRP6-M2-immunized group was slightly delayed and required almost 11 days to form ∼4-mm tumors. The total number of blood vessels around each implant site from pCR3.1-VS-HSP65-TP-GRP6-M2-immunized mice was significantly lower than that from the saline group (22 ± 4 versus 72 ± 14; P < 0.01) or from non-GRP-containing plasmid-immunized mice (22 ± 4 versus 63 ± 19; P < 0.01). To further test the efficacy of the anti-GRP vaccine, the extent of lung metastasis by intravenously administered tumor cells in the tail vein of immunized mice was evaluated. Metastatic tumor nodules were often detected in the lungs 21 days after injection of tumor cells. The average weight of lungs of mice immunized with pCR3.1-VS-HSP65-TP-GRP6-M2 was significantly lower than that of the saline group (0.215 ± 0.020 g versus 0.301 ± 0.068 g; P < 0.05) or the pCR3.1-VS-HSP65-TP-M2 control group (0.215 ± 0.020 g versus 0.289 ± 0.087 g; P < 0.05), which indicates that fewer metastases were formed in the lungs of the anti-GRP DNA vaccine-immunized group. In addition, the average number of metastatic nodules in mice immunized with pCR3.1-VS-HSP65-TP-GRP6-M2 was significantly less than that in mice that received saline (37.2 ± 9.4 versus 88.0 ± 22.6; P < 0.001) or in mice in the pCR3.1-VS-HSP65-TP-M2 control group (37.2 ± 9.4 versus 79.3.0 ± 16.8; P < 0.001) (Fang et al., 2009).
References
Fang et al., 2009: Fang J, Lu Y, Ouyang K, Wu G, Zhang H, Liu Y, Chen Y, Lin M, Wang H, Jin L, Cao R, Roque RS, Zong L, Liu J, Li T. Specific antibodies elicited by a novel DNA vaccine targeting gastrin-releasing peptide inhibit murine melanoma growth in vivo. Clinical and vaccine immunology : CVI. 2009; 16(7); 1033-1039. [PubMed: 19458203].