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Vaccine Detail
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MUC1-STn(T6)-OVA323-339 vaccine |
| Vaccine Information |
- Vaccine Name: MUC1-STn(T6)-OVA323-339 vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (20 aa, PAHGVTSAPDTRPAPGSTAP), STn at T6 (Westerlind et al., 2008)
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Adjuvant:
CFA/IFA (Westerlind et al., 2008)
- Immunization Route: subcutaneous injection
- Description: A fully synthetic conjugate vaccine consisting of tumor-associated MUC1 tandem repeat glycopeptide (sequence: PAHGVTSAPDTRPAPGSTAP) bearing STn at Thr6 (all constructs) and Tn at additional threonines in di- and triglycosylated variants, linked via a nonimmunogenic spacer to the OVA323-339 T-cell epitope. OVA323-339 activates CD4+ T helper cells via TCR/MHCII on antigen-presenting cells, overcoming the poor intrinsic immunogenicity of MUC1 glycopeptides. Three constructs were tested: monoglycosylated (1, STn at Thr6), diglycosylated (2, STn + Tn), and triglycosylated (3, STn + Tn at two positions including the immunodominant PDTRP motif). Administered subcutaneously with CFA/IFA in DO11.10 transgenic mice (10 µg/mouse), vaccines 1 and 2 induced highly specific humoral immune responses (1/3 and 2/3 mice respectively), with high antibody titers after the third immunization that did not increase with further boosting. Vaccine 3 elicited no response (0/3), indicating glycosylation within PDTRP abolishes immunogenicity. ELISA using BSA conjugates of non- (19), mono- (20), di- (21), and triglycosylated (22) MUC1 peptides showed strong antibody binding to glycosylated but not non-glycosylated MUC1-BSA (19), confirming both saccharide and peptide backbone are required for epitope recognition. Antibodies from vaccines 1 and 2 also recognized triglycosylated conjugate 22 (Tn in PDTRP) despite vaccine 3 being non-immunogenic, suggesting peptide backbone accessibility dominates epitope recognition. Vaccine 1 exhibited the highest binding affinity across all tumor-associated glycopeptide-BSA conjugates (Westerlind et al., 2008).
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| Host Response |
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| References |
Westerlind et al., 2008: Westerlind U, Hobel A, Gaidzik N, Schmitt E, Kunz H. Synthetic vaccines consisting of tumor-associated MUC1 glycopeptide antigens and a T-cell epitope for the induction of a highly specific humoral immune response. Angewandte Chemie (International ed. in English). 2008; 47(39); 7551-7556. [PubMed: 18704911].
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