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Vaccine Detail

Qβ-MUC1-β-Tf Conjugate Vaccine
Vaccine Information
  • Vaccine Name: Qβ-MUC1-β-Tf Conjugate Vaccine
  • Target Pathogen: Cancer
  • Target Disease: Cancer
  • Type: Conjugate vaccine
  • Status: Research
  • Host Species for Licensed Use: Mouse
  • Antigen: MUC1 (Wu et al., 2021)
  • Adjuvant: MPLA (Wu et al., 2021)
  • Immunization Route: subcutaneous injection
  • Description: A synthetic glycopeptide-VLP conjugate vaccine containing a MUC1 glycopeptide bearing an unnatural beta-linked Thomsen-Friedenreich (Tf) disaccharide [(beta)Gal-(1,3)-(beta)GalNAc] covalently conjugated to bacteriophage Q(beta) virus-like particles (~220 glycopeptides per capsid), with potential antineoplastic activity. The unnatural beta-glycosyl linkage provides significantly enhanced stability toward glycosidase degradation (no detectable cleavage after 24 hours versus near-complete cleavage of the natural alpha-linked MUC1-Tf glycopeptide within 1.75 hours). Vaccination with Q(beta)-MUC1-(beta)-Tf conjugate with MPLA adjuvant successfully overcame MUC1 immune tolerance in human MUC1 transgenic mice, inducing high IgG antibody titers (mean 2,200,000 ELISA units, >1,000-fold over control) encompassing all major IgG subtypes with both Th1 and Th2 activation. The induced antibodies demonstrated complement-mediated cytotoxicity toward MUC1-expressing melanoma tumor cells equivalent to those induced by the natural MUC1-alpha-Tf vaccine. MUC1 antigen, a membrane-bound glycoprotein overexpressed in aberrant or hypoglycosylated form in multiple cancers including breast, lung, pancreatic, colon, prostate, and ovarian cancers (Wu et al., 2021).
Host Response
References
Wu et al., 2021: Wu X, McFall-Boegeman H, Rashidijahanabad Z, Liu K, Pett C, Yu J, Schorlemer M, Ramadan S, Behren S, Westerlind U, Huang X. Synthesis and immunological evaluation of the unnatural β-linked mucin-1 Thomsen-Friedenreich conjugate. Organic & biomolecular chemistry. 2021; 19(11); 2448-2455. [PubMed: 33645601].