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Vaccine Detail
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Self-Adjuvanting AuNP MUC1 Glycopeptide Vaccine with S-Glycosidic Linkage (SThr) and (4S)-4-fluoro-L-proline |
| Vaccine Information |
- Vaccine Name: Self-Adjuvanting AuNP MUC1 Glycopeptide Vaccine with S-Glycosidic Linkage (SThr) and (4S)-4-fluoro-L-proline
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (HGVTSAPDS(Thr)RPAPGSTAPPA) (Compañón et al., 2019)
- Immunization Route: subcutaneous injection
- Description: A synthetic MUC1 glycopeptide vaccine consisting of doubly engineered glycopeptide 12 conjugated to PEGylated gold nanoparticles (~200 glycopeptides/AuNP, AuNP-12) administered without exogenous adjuvant. Glycopeptide 12 comprises the complete MUC1 tandem repeat sequence incorporating S-(α-D-GalNAc)-thiothreonine (SThr*, O→S substitution at the glycosidic linkage) and (4S)-4-fluoro-L-proline (fPro) substitutions. The O→S substitution increases carbohydrate-peptide distance, eliminates water-mediated peptide-carbohydrate hydrogen bonds, and shifts glycosidic linkage geometry (φ/ψ ≈ 65°/70°), preorganizing the peptide into a folded conformation optimal for anti-MUC1 antibody binding, confirmed by SPR on model epitope peptide 2* (KD = 168 μM vs 619 μM for native O-glycopeptide and 3480 μM for unglycosylated epitope, ~20-fold improved affinity). The fPro substitution enhances antigen-antibody enthalpic interactions. Immunization of BALB/c mice (n=5) with prime plus three booster doses (2 μg/dose, 21-day intervals) elicited significant anti-MUC1 IgG responses (predominantly IgG1, Th2-type), with non-negligible IgM and weak IgG2a/IgG2b/IgG3 titers, class-switch recombination without CD4+ T-cell epitope or exogenous adjuvant, exceeding titers of AuNP-based formulations requiring Freund's adjuvant. Antisera selectively recognized tumor-associated MUC1 on MCF-7 and T47D breast cancer cells but not HEK293T cells, and positively stained breast cancer patient biopsies with no staining in healthy tissue (Compañón et al., 2019).
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| References |
Compañón et al., 2019: Compañón I, Guerreiro A, Mangini V, Castro-López J, Escudero-Casao M, Avenoza A, Busto JH, Castillón S, Jiménez-Barbero J, Asensio JL, Jiménez-Osés G, Boutureira O, Peregrina JM, Hurtado-Guerrero R, Fiammengo R, Bernardes GJL, Corzana F. Structure-Based Design of Potent Tumor-Associated Antigens: Modulation of Peptide Presentation by Single-Atom O/S or O/Se Substitutions at the Glycosidic Linkage. Journal of the American Chemical Society. 2019; 141(9); 4063-4072. [PubMed: 30726084].
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