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Vaccine Detail
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MUC1 9VNTR Adenoviral Vector Prime Protein Boost (VPP) Vaccine |
| Vaccine Information |
- Vaccine Name: MUC1 9VNTR Adenoviral Vector Prime Protein Boost (VPP) Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Recombinant vector/protein subunit
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 9VNTR MUC1 (9×HGVTSAPDTRPAPGSTAPPA) (Wang et al., 2014)
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Adjuvant:
DDA/MPL (Wang et al., 2014)
- Immunization Route: Intramuscular and subcutaneous
- Description: A heterologous prime-boost vaccine (MUC1 VPP) of recombinant adenovirus expressing nine MUC1 VNTR tandem repeats (AD-9M), generated via AdMax™ homologous recombination in HEK293 cells, administered intramuscularly on day 3, followed by His-tagged 9M protein (50 µg, HiTrap-purified) adjuvanted with DDA/MPL (250 µg DDA + 25 µg MPL) subcutaneously on days 10 and 17, evaluated in a B16 murine melanoma model (C57BL/6 mice). The antigen comprises nine 20 amino acid VNTR tandem repeats (HGVTSAPDTRPAPGSTAPPA) of MUC1, overexpressed ~5-fold in B16 cells and ~200-fold in implanted tumors versus normal C2C12 cells. DDA/MPL significantly enhanced humoral immunity versus all control groups and enhanced IFN-γ-secreting T cells ~3-fold and CTL activity using MHC-I H-2Db restricted peptide SAPDTRPAP at 100:1 ratio; 9M alone showed no significant antibody or IFN-γ response above PBS. VPP achieved 59.45% tumor weight inhibition (p<0.05), with tumor weights of 1.18±0.78 g (VPP), 2.24±2.27 g (AD-9M) and 3.08±1.00 g (PBS), versus 39.86% for AD-9M alone, with mean survival extended from 27 days (PBS) to 37 days (VPP) versus 33 days (AD-9M). Lymphocyte proliferation by CFSE was 28.68% (VPP), 14.26% (AD-9M) and 8.49% (PBS). IL-2 reached ~382 pg/ml in VPP, 13-fold above PBS and 2.5-fold above AD-9M, indicating Th1 predominance; both groups elicited ~6-fold higher IL-10 than PBS, with VPP IL-10 at 60.5 pg/ml. VPP IFN-γ-secreting T cells increased 2-fold overall. Survival was significantly prolonged with 33.33% of VPP mice surviving to day 50 versus 0% in control groups by days 36–38 (p<0.05); AD-9M survival was 22.22%. Homologous 9M+DDA/MPL prime-boost did not achieve significant tumor inhibition or survival benefit, with mean survival times of 32–34 days (Wang et al., 2014).
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| Host Response |
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| References |
Wang et al., 2014: Wang Y, Liu C, Xia Q, Wang P, Li B, Lu Z, Sun J, Wu H, Yu B, Wu J, Yu X, Kong W, Zhang H, Cong X. Antitumor effect of adenoviral vector prime protein boost immunity targeting the MUC1 VNTRs. Oncology reports. 2014; 31(3); 1437-1444. [PubMed: 24378623].
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