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Vaccine Detail
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MUC1-Tn/gamma-PGA Multilayer Self-Assembly Nanovaccine |
| Vaccine Information |
- Vaccine Name: MUC1-Tn/gamma-PGA Multilayer Self-Assembly Nanovaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Nanoconjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (20 aa, HGVTSAPDTRPAPGSTAPPA), Tn at T9, S15 (Liu et al., 2015)
- Immunization Route: Intraperitoneal injection (i.p.)
- Description: A multilayer self-assembling glycopeptide nanovaccine (V1, spherical by TEM) assembled via electrostatic interactions at 1:7:1 molar ratio (P1:γ-PGA:P2), shaken 5 min and diluted 1:10 in PBS to 54 μM: (1) tetanus toxoid-derived Th epitope peptide P1 with seven N-terminal lysine residues forming positively charged core (+15 mV, ~190 nm); (2) γ-PGA (MW 50–100 kD) as negatively charged immunostimulant inner layer (−28 mV); and (3) MUC1 glycopeptide P2 bearing Tn antigen at Thr9 and Ser15 (PDTRP/GSTAP motifs) as outer layer (−20 mV at equivalent P2, −13 mV at 2-fold P2). Negative controls V3 (P3+γ-PGA+P4, both Th and B cell epitopes lacking seven lysine residues, ~255 nm) and V4 (P1+P2 lacking γ-PGA, ~255 nm) and covalent positive control V5 were included. In vitro, CF-V1 was internalized by RAW264.7 macrophages concentration- (7–54 μM, 90 min) and time-dependently (5–90 min, 54 μM) by flow cytometry; 54 μM V1 stimulation for 48 h significantly elevated IL-6 and IL-12 vs PBS, with LPS (10 μg/mL) as positive control. In vivo, Balb/c mice (n=4/group) received five biweekly i.p. injections (100 μL, 25 μg MUC1/dose), generating anti-MUC1 IgG titers of 5200, comparable to V5; V3 and V4 elicited negligible responses; V2 (V1+Freund's adjuvant) paradoxically weakened responses, suggesting disruption of self-assembly. Predominantly IgG2a and IgM isotypes indicated Th1-skewed immunity via IL-12→IFN-γ→B cell differentiation. Induced antisera strongly bound MCF-7 breast tumor cells by FACS (negligible for V3/V4) and effectively killed MCF-7 cells via complement-dependent cytotoxicity (CDC) by MTT assay, with no killing in complement-negative controls (Liu et al., 2015).
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| Host Response |
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| References |
Liu et al., 2015: Liu YF, Sun ZY, Chen PG, Huang ZH, Gao Y, Shi L, Zhao YF, Chen YX, Li YM. Glycopeptide Nanoconjugates Based on Multilayer Self-Assembly as an Antitumor Vaccine. Bioconjugate chemistry. 2015; 26(8); 1439-1442. [PubMed: 26108637].
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