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Vaccine Detail

MUC1-Tn alpha/beta-Glycopeptide AuNP Vaccine
Vaccine Information
  • Vaccine Name: MUC1-Tn alpha/beta-Glycopeptide AuNP Vaccine
  • Target Pathogen: Cancer
  • Target Disease: Cancer
  • Type: Conjugate vaccine
  • Status: Research
  • Host Species for Licensed Use: Mouse
  • Antigen: MUC1 VNTR (20-mer, AHGVTSAPDTRPAPGSTAPP), Tn at T10 (Gibadullin et al., 2025)
  • Immunization Route: subcutaneous injection
  • Description: A synthetic α/β-glycopeptide-gold nanoparticle vaccine composed of backbone-modified MUC1-derived glycopeptides multivalently conjugated (~200 copies/particle) to PEGylated AuNPs (~13 nm), formulated in PBS, adjuvant-free. Three glycopeptide analogs were evaluated: two variants with four β^3-homoamino acid substitutions outside the immunodominant APDTRP epitope (AuNP-10 and AuNP-12) and one variant with four β³ substitutions, three outside and one within APDTRP at the A7 position (AuNP-13). In BALB/c mice (n=5) immunized subcutaneously with prime plus three boosters at 14-day intervals (2 μg/dose), the two variants with substitutions outside APDTRP achieved ~100-fold enhanced proteolytic stability (t½ ~124 and ~118 min vs. ~1.0 min), elicited similar or superior anti-MUC1 IgG with full cross-reactivity toward the natural antigen, and induced elevated or comparable IFNγ with no detectable IL-4, confirming Th1-biased cellular immunity. The variant with an A7 substitution within APDTRP showed ~30-fold stability improvement but reduced cross-reactivity toward the natural antigen, only slightly lower antibody responses, and negligible IFNγ, demonstrating that epitope backbone modification impairs MHC I presentation. Antibody titers peaked after the first booster. Antisera from AuNP-10, the variant that induced the highest IFNγ levels among the unnatural conjugates, positively stained TA-MUC1-expressing MCF7 (breast) and DLD-1 (colorectal) cancer cell lines but not MUC1-negative HEK293T cells (Gibadullin et al., 2025).
Host Response
References
Gibadullin et al., 2025: Gibadullin R, Suárez Ó, Lazaris FS, Gutiez N, Atondo E, Araujo-Aris S, Eguskiza A, Niu J, Kuhn AJ, Grosso AS, Rodriguez H, García-Martín F, Marcelo F, Santos T, Avenoza A, Busto JH, Peregrina JM, Gellman SH, Anguita J, Fiammengo R, Corzana F. Enhancing Cancer Vaccine Efficacy: Backbone Modification with β‑Amino Acids Alters the Stability and Immunogenicity of MUC1-Derived Glycopeptide Formulations. JACS Au. 2025; 5(5); 2270-2284. [PubMed: 40443897].