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Vaccine Detail

AuNP-MUC1-Tn Vaccine with (2S,3R)-3-hydroxynorvaline
Vaccine Information
  • Vaccine Name: AuNP-MUC1-Tn Vaccine with (2S,3R)-3-hydroxynorvaline
  • Target Pathogen: Cancer
  • Target Disease: Cancer
  • Type: Conjugate vaccine
  • Status: Research
  • Host Species for Licensed Use: Mouse
  • Antigen: MUC1 (Bermejo et al., 2024)
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Description: A synthetic gold nanoparticle-conjugated glycopeptide vaccine containing MUC1 VNTR-derived Tn antigen (α-O-GalNAc) with (2S,3R)-3-hydroxynorvaline replacing threonine at the APDTRP immunodominant epitope, with potential antineoplastic activity. Vaccination with AuNP-MUC1-Tn with (2S,3R)-3-hydroxynorvaline elicits anti-MUC1 IgG antibody responses comparable to the natural threonine-containing variant (KD: 17 μM vs 19 μM for SM3 antibody binding). Immune responses are predominantly Th2-type with high IgG1 and low IgM/IgG2a/IgG2b/IgG3 levels. The unnatural amino acid enhances CH/π interactions with anti-MUC1 antibodies (4.2Å vs 4.7Å), and the SM3 antibody binding affinity correlates with immunogenic response in vivo, demonstrating structure-based vaccine design principles. PEGylated gold nanoparticles serve as both carrier and self-adjuvant. Antibodies elicited exhibit cross-reactivity with natural tumor-associated MUC1 and selectively target human breast cancer cells expressing aberrantly glycosylated MUC1 (Bermejo et al., 2024).
Host Response
References
Bermejo et al., 2024: Bermejo IA, Guerreiro A, Eguskiza A, Martínez-Sáez N, Lazaris FS, Asín A, Somovilla VJ, Compañón I, Raju TK, Tadic S, Garrido P, García-Sanmartín J, Mangini V, Grosso AS, Marcelo F, Avenoza A, Busto JH, García-Martín F, Hurtado-Guerrero R, Peregrina JM, Bernardes GJL, Martínez A, Fiammengo R, Corzana F. Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses. JACS Au. 2024; 4(1); 150-163. [PubMed: 38274250].