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Vaccine Detail
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MUC1 Tn/T-T9 Glycopeptide-BSA Conjugate Vaccine |
| Vaccine Information |
- Vaccine Name: MUC1 Tn/T-T9 Glycopeptide-BSA Conjugate Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (20 aa, HGVTSAPDTRPAPGSTAPPA); Tn at T9/ T at T9 / Tn at T9 + T at S15
- Immunization Route: subcutaneous injection
- Description: A synthetic glycopeptide conjugate vaccine comprising the MUC1 variable number tandem repeat sequence (20 aa, HGVTSAPDTRPAPGSTAPPA) bearing Tn antigen (GalNAc-α-O) and/or T antigen (Galβ1-3GalNAc-α-O) at positions T9 (threonine 9, within the immunodominant PDTRP motif) and/or S15 (serine 15), conjugated to bovine serum albumin (BSA) carrier protein via an N-terminal triethylene glycol (TEG) spacer using squaric acid chemistry, with 8–12 glycopeptide molecules per BSA. Glycopeptides were synthesized by microwave-assisted Fmoc solid-phase peptide synthesis. MUC1, a type I transmembrane glycoprotein overexpressed in aberrantly truncated glycosylation form in most epithelial tumor tissues including breast, pancreatic, and ovarian cancers, exposes tumor-associated carbohydrate antigens (Tn, T) and backbone peptide epitopes including the immunodominant PDTRP motif when O-glycosylation is truncated. BSA served as a carrier protein to enhance immunogenicity of the otherwise poorly immunogenic glycopeptide B-cell epitopes. In BALB/c mice (n=4), glycosylation at T9 drove the highest IgG responses across all conjugate variants, with Tn and T antigens at T9 showing comparable immunogenicity; S15 glycosylation alone was insufficient for high immune response. Addition of Alum adjuvant (MUC1-BSA+Alum) was superior to MUC1-BSA alone, generating progressively increasing antibody titers across three immunizations, a Th2-biased response (IgG1 dominant; IgG1/IgG2a/IgG2b/IgG3/IgM/IgA detected), and MUC1-specific plasma antibodies that recognized MUC1-positive tumor cells MCF-7 and B16-MUC1 (p<0.0001) but showed no significant binding to MUC1-negative B16-F10 cells. MUC1-BSA+Alum additionally induced partial CD8+ T cell IFN-γ secretion (p≤0.001), while MUC1-BSA alone showed no significant cellular immune response (Wu et al., 2024).
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| Host Response |
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| References |
Wu et al., 2024: Wu Y, Zhou Y, Guo Y, Ling Y, Li Y, Cai H. Protocol to prepare MUC1 glycopeptide vaccines and evaluate immunization effects in mice. STAR protocols. 2024; 5(2); 103047. [PubMed: 38691463].
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