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Vaccine Detail
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Hyperbranched Polyglycerol (HPG)-MUC1 dual-Tn glycopeptide–P2 vaccine |
| Vaccine Information |
- Vaccine Name: Hyperbranched Polyglycerol (HPG)-MUC1 dual-Tn glycopeptide–P2 vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (PAHGVTSAPDTRPAPGSTAPPA) (Glaffig et al., 2015)
- Immunization Route: Subcutaneous and intraperitoneal
- Description: A fully synthetic multivalent antitumour vaccine comprising a tumour-associated MUC1 glycopeptide B-cell epitope (PAHGVTSAPDTRPAPGSTAPPA) carrying Tn antigens at Ser-17 and Thr-11, glycosylating both immunodominant PDTRP and GSTA motifs to enhance tumour selectivity, conjugated to tetanus toxoid-derived T-cell epitope P2 (QYIKANSKFIGITEL) via oligoethylene glycol spacers, and coupled to a hyperbranched polyglycerol (HPG) carrier (Mn = 2410 g/mol) bearing ~8 antigen binding sites via copper-catalysed azide–alkyne cycloaddition, forming >10 nm spherical particles suitable for dendritic cell uptake. In BALB/c mice immunised three times over four weeks (subcutaneous CFA priming, two intraperitoneal IFA boosts), vaccine 1 (~8 sites, dual Tn) elicited significantly higher, consistent IgG titres earlier (day 33) than lower-valency vaccine 2 (~5 sites, single Tn; day 47), among the highest for fully synthetic vaccines though below TTox-based vaccines (500,000–1 million), and superior to linear P(HPMA)-based vaccines. Isotype analysis showed predominantly IgG1 (MHC-II-mediated, immunological memory), elevated IgM, and IgG2a/IgG2b capable of ADCC and CDC, the latter absent in vaccine 2 animals. Flow cytometry demonstrated consistently strong binding to MUC1-expressing T47D breast tumour cells across all vaccine 1 antisera (70%, 87%, 88%) versus variable binding from vaccine 2 (11%, 47%, 85%) (Glaffig et al., 2015).
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| Host Response |
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| References |
Glaffig et al., 2015: Glaffig M, Palitzsch B, Stergiou N, Schüll C, Strassburger D, Schmitt E, Frey H, Kunz H. Enhanced immunogenicity of multivalent MUC1 glycopeptide antitumour vaccines based on hyperbranched polymers. Organic & biomolecular chemistry. 2015; 13(40); 10150-10154. [PubMed: 26299280].
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