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Vaccine Detail
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MUC1-Tn–P30–AuNP Three-Component Vaccine |
| Vaccine Information |
- Vaccine Name: MUC1-Tn–P30–AuNP Three-Component Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (APPAHGVTSAPRTDPASTVGH) (Cai et al., 2016)
- Immunization Route: subcutaneous injection
- Description: A three-component nanoparticle-conjugate glycopeptide vaccine consisting of synthetic MUC1 tandem repeat glycopeptides carrying three tumor-associated Tn antigens per peptide, covalently linked to the CD4+ T-cell helper epitope P30 (from Tetanus Toxoid), and conjugated to PEGylated gold nanoparticles (AuNPs, 13 nm citrate-capped core, final hydrodynamic diameter ~30 nm) via a heterobifunctional NHS/maleimido linker at high peptide density (500–1400 peptides/AuNP). The design aims at promoting antigen presentation on antigen presenting cells (APCs), increased T-cell activation, and MHC-II restricted T- and B-cell cooperation. Administered with Complete Freund's Adjuvant (CFA) with three booster immunizations at 21-day intervals in wild-type Balb/c mice, and compared against a two-component MUC1–P30 glycopeptide conjugate control (formulation 8) administered at approximately 10-fold higher peptide dose. The AuNP-based formulation induced significant MHC-II mediated immune responses in all three immunized mice, with antibody titers comparable to the two-component control despite the ~10-fold lower peptide dose, suggesting that multivalent presentation of the glycopeptide antigen on AuNPs increases antigen stability in vivo and enhances antigen presentation efficiency. Antibody isotype analysis revealed mixed IgG1, IgG2a, and IgG2b responses in 2 out of 3 mice, indicating partial isotype switching from Th2-mediated (IgG1) toward Th1-mediated (IgG2a, IgG2b) responses, in contrast to the two-component control which induced predominantly IgG1 antibodies. FACS analysis confirmed that antisera from 2 out of 3 immunized mice recognized aberrantly glycosylated MUC1 on human MCF-7 breast cancer cells (66% and 72% cell staining respectively), with 5 out of 6 animals across both formulations producing polyclonal antisera that recognized tumor-associated MUC1 on human breast cancer cells (Cai et al., 2016).
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| Host Response |
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| References |
Cai et al., 2016: Cai H, Degliangeli F, Palitzsch B, Gerlitzki B, Kunz H, Schmitt E, Fiammengo R, Westerlind U. Glycopeptide-functionalized gold nanoparticles for antibody induction against the tumor associated mucin-1 glycoprotein. Bioorganic & medicinal chemistry. 2016; 24(5); 1132-1135. [PubMed: 26853835].
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