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Vaccine Detail
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Self-Adjuvanting MUC1-PADRE-Pam3CysSer Tricomponent Vaccines (unglycosylated/Tn/T) |
| Vaccine Information |
- Vaccine Name: Self-Adjuvanting MUC1-PADRE-Pam3CysSer Tricomponent Vaccines (unglycosylated/Tn/T)
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Wilkinson et al., 2012)
- Immunization Route: Intradermal injection (i.d.)
- Description: A fully synthetic self-adjuvanting tricomponent vaccine consisting of the 20-amino acid MUC1 VNTR domain covalently conjugated to the universal T-cell helper peptide PADRE and the lipopeptide immunoadjuvant Pam3CysSer. Three variants were prepared: unglycosylated (vaccine 1), bearing five Tn antigens (vaccine 2), or five T antigens (vaccine 3). The vaccines spontaneously self-assemble into nanoparticles (17-25 nm) in aqueous solution. Vaccination elicited robust antibody responses without external adjuvants, with IgG titers of 1775-8400; unglycosylated (8,400) > Tn (3,000) > T (1,775). Antibodies showed no cross-reactivity between variants. The response was Th2-skewed (IgG1 > IgG2c) with high IgG3 levels (1,000-4,000), suggesting multivalent presentation effects. Sera antibodies bound to MCF7 breast cancer cells and B16.MUC1 melanoma cells. Pam?CysSer acts as a TLR1-TLR2 agonist providing self-adjuvanting activity. MUC1 antigen, a membrane-bound glycoprotein, is overexpressed in an aberrant or deglycosylated form in over 90% of solid tumors including cancers of the breast, prostate, pancreas, and ovary (Wilkinson et al., 2012).
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| Host Response |
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| References |
Wilkinson et al., 2012: Wilkinson BL, Day S, Chapman R, Perrier S, Apostolopoulos V, Payne RJ. Synthesis and immunological evaluation of self-assembling and self-adjuvanting tricomponent glycopeptide cancer-vaccine candidates. Chemistry (Weinheim an der Bergstrasse, Germany). 2012; 18(51); 16540-16548. [PubMed: 23090901].
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