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Vaccine Detail
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Sialylated MUC1-Tn Glycopeptide-BSA Conjugate Vaccine |
| Vaccine Information |
- Vaccine Name: Sialylated MUC1-Tn 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), STn or 2,6-ST at S15, Tn or T at T9 (Cai et al., 2012)
- Immunization Route: subcutaneous injection
- Description: A conjugate vaccine composed of synthetic MUC1 tandem repeat glycopeptides (HGVTSAPDTRPAPGSTAPPA) bearing tumor-associated sialylated carbohydrate antigens STn or 2,6-ST at serine 15 (S15) and Tn or T antigen at threonine 9 (T9) within the immunodominant PDTRP epitope, covalently conjugated to bovine serum albumin (BSA) as the carrier protein via a squaric acid linker, with a triethylene glycol spacer at the N-terminus. Glycopeptides were synthesized by microwave-supported Fmoc solid-phase peptide synthesis on 2-chlorotrityl resin with an average loading of nine glycopeptide molecules per BSA molecule. Subcutaneous immunization of Balb/c mice (10 µg/dose) with Complete Freund’s Adjuvant (primary) and Incomplete Freund’s Adjuvant (boosters) induced strong antibody responses across all six vaccine constructs (23–28), with ELISA titers of ~6,000–30,000 (endpoint 51,200–204,800), unexpectedly exceeding prior sialylated BSA conjugate vaccines which showed low immunogenicity and a related STn/Tn-OVA construct which showed no immunogenicity. IgG1 was the predominant isotype with IgM also present, consistent with establishment of immunological memory, with additional IgG2a/b, IgG3, and IgA antibodies also induced; elevated IgM and IgA relative to tetanus toxoid conjugates was attributed to the BSA carrier. FACS analysis of MCF-7 human breast tumor cell binding demonstrated that glycosylation at T9 within the PDTRP epitope was a major determinant of tumor selectivity: vaccines 24–28 bearing Tn or T antigen at T9 showed strong MCF-7 binding, while vaccines 23 and 26 lacking T9 glycosylation showed weak binding despite high antibody titers. Non-glycosylated vaccine 1 (from prior study, included as comparator) also showed weak MCF-7 binding. The weak MCF-7 binding of vaccine 23 (STn at S15 only) was particularly surprising given that a closely related tetanus toxoid conjugate had previously induced strong tumor cell recognition. These findings establish BSA as a viable and cost-effective alternative to tetanus toxoid as carrier protein in exploratory MUC1 antitumor vaccine studies (Cai et al., 2012).
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| Host Response |
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| References |
Cai et al., 2012: Cai H, Huang ZH, Shi L, Sun ZY, Zhao YF, Kunz H, Li YM. Variation of the glycosylation pattern in MUC1 glycopeptide BSA vaccines and its influence on the immune response. Angewandte Chemie (International ed. in English). 2012; 51(7); 1719-1723. [PubMed: 22247051].
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