|
|
Vaccine Detail
|
di-Man-MUC1-Tn-TTox Vaccine |
| Vaccine Information |
- Vaccine Name: di-Man-MUC1-Tn-TTox Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 22-mer MUC1 VNTR (PAHGVTSAPDTRPAPGSTAPPA) (Glaffig et al., 2018)
- Immunization Route: Intraperitoneal injection (i.p.)
- Description: A synthetic MUC1 glycopeptide-tetanus toxoid conjugate vaccine composed of a 22-mer MUC1 tandem repeat glycopeptide (PAHGVTSAPDTRPAPGSTAPPA) incorporating the Tn antigen at Ser17, with covalently linked divalent mannose ligands at the N-terminus via a terminal lysine, conjugated to tetanus toxoid (150 kDa) through a squarate linker, containing on average 73 MUC1 glycopeptides per TTox molecule. The mannose ligands target mannose receptors CD206 and CD209 on MØs and DCs, facilitating receptor-mediated endocytosis and enhanced MHC II-restricted antigen presentation to CD4+ T helper cells; mannosylated vaccines have been reported to improve APC uptake by 2-4 orders of magnitude. Dose-dependent CD206+ MØ binding was confirmed by FACS using a Cy3-labeled divalent mannose-dye conjugate (~20% at 0.0125 μg/mL; >40% at 0.1 μg/mL). Groups of three BALB/c mice received one initial immunization and three intraperitoneal boosts with PBS and IFA (4 weeks, then 2-week intervals); blood collected 5 days post-boost. The mannosylated vaccine induced 7.5-fold higher IgG titers than the non-mannosylated reference (endpoint titers 1/1×10⁶ vs 1/2×10⁵, p<0.01), enhancing both early IgM and adapted IgG responses. Predominantly IgG1 antibodies were induced alongside IgG2a and IgG2b, the latter mediating ADCC and CDC. Induced antibodies bound similarly to MUC1 on human MCF-7 breast cancer cells regardless of mannosylation. Vaccination increased F4/80⁺/CD11b⁺ MØs, CD11c⁺ DCs, and CD4+ T helper cells in the spleen, abdomen, and inguinal lymph nodes. Tetravalent mannose conjugates showed superior macrophage binding over divalent, suggesting higher valency improves mannose receptor engagement (Glaffig et al., 2018).
|
| Host Response |
|
|
| References |
Glaffig et al., 2018: Glaffig M, Stergiou N, Hartmann S, Schmitt E, Kunz H. A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells. ChemMedChem. 2018; 13(1); 25-29. [PubMed: 29193802].
|
|
