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Vaccine Detail
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MUC1 beta-GalNAc-Thr Glycopeptide-BSA Vaccine |
| Vaccine Information |
- Vaccine Name: MUC1 beta-GalNAc-Thr Glycopeptide-BSA Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 10-mer MUC1 (SAPDTRPAPG), Tn at T5 (Leiria et al., 2017)
- Immunization Route: subcutaneous injection
- Description: A synthetic MUC1 glycopeptide conjugate vaccine composed of the 10-residue tandem repeat-derived sequence NHAcSAPDT[βGalNAc]RPAPG conjugated to BSA (glycopeptide 4-BSA), bearing βGalNAc-Thr as an unnatural Tn antigen isomer absent in normal and tumor mammalian cells, suggesting potential evasion of immune tolerance. The glycopeptide was assembled by Fmoc-based solid-phase peptide synthesis and conjugated to BSA via EDC/NHS chemistry, yielding one to two epitopes per BSA molecule. Upon immunization of Balb/c mice with CFA/IFA, glycopeptide 4-BSA induced serum antibody titers of 1:320,000 by ELISA (8-fold higher than αGalNAc counterpart glycopeptide 3-BSA at 1:40,000). BSA depletion confirmed 4-BSA antisera were enriched in epitope-specific antibodies. Flow cytometry showed anti-glycopeptide 4-BSA antibodies bound MCF-7 breast tumor cells at 54% positive staining at 1:400 dilution versus 37% for anti-glycopeptide 3-BSA. Immunopurified anti-βGalNAc antibodies cross-recognized αGalNAc-glycopeptide (absorbance ~1.0) and vice versa (~0.8), with both populations binding asialo-submaxillary mucin. Molecular dynamics simulations at χ1 +60° confirmed both isomers interact with SM3 via hydrogen bonds with Y32L and N53L (PDB: 1SM3). SPR confirmed βGalNAc-glycopeptide 4 binding to SM3 (KD ≈ 20 µM), comparable to the unglycosylated peptide (KD 24 µM), versus αGalNAc-glycopeptide 3 (KD ≈ 52 nM), representing meaningful binding despite ~400-fold lower affinity (Leiria et al., 2017).
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| Host Response |
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| References |
Leiria et al., 2017: Leiria Campo V, Riul TB, Oliveira Bortot L, Martins-Teixeira MB, Fiori Marchiori M, Iaccarino E, Ruvo M, Dias-Baruffi M, Carvalho I. A Synthetic MUC1 Glycopeptide Bearing βGalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells. Chembiochem : a European journal of chemical biology. 2017; 18(6); 527-538. [PubMed: 28068458].
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