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Vaccine Detail
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TLR7a-BSA-MUC1 Self-Adjuvanting Conjugate Vaccine |
| Vaccine Information |
- Vaccine Name: TLR7a-BSA-MUC1 Self-Adjuvanting Conjugate Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Du et al., 2020)
- Immunization Route: Intraperitoneal injection (i.p.)
- Description: A self-adjuvanting protein conjugate vaccine containing MUC1 glycopeptide (GVTSAPDTRPAPG with Tn antigen at threonine in PDTRP motif) and a small-molecule TLR7 agonist covalently conjugated to bovine serum albumin (BSA), with 9-11 copies of the glycopeptide per BSA molecule. The vaccine utilizes a three-in-one design where both the adjuvant and tumor-associated antigen are conjugated to the same carrier protein. Covalent conjugation of the TLR7 agonist to the carrier protein enhances immune stimulation through cluster effects, prevents adjuvant systemic toxicity, and facilitates codelivery of adjuvants and antigens to lymph nodes. Vaccination (21 ?g MUC1 per injection on days 1, 15, and 29) elicited IgG antibody titers 500-fold higher than no adjuvant control, 100-fold higher than mixed TLR7a, and 15-fold higher than traditional adjuvants (MPLA, Pam3CSK4). The vaccine induced Th1-skewed immune responses with highest IgG2a titers and balanced IgG1/IgG2a/IgG2b/IgG3 production, along with 4-10-fold increased IFN-? and IL-6 secretion. Antibodies induced bind MUC1-expressing cancer cells (MCF-7, B16-MUC1) with minimal binding to MUC1-negative cells (B16-F10) (tumor binding validates epitope relevance, but absolute binding levels are formulation-dependent), mediate complement-dependent cytotoxicity reducing MCF-7 viability to <40%, and elicit potent cytotoxic T-lymphocyte responses. Progressive IgG increase with IgM plateau demonstrated successful antibody class switching. MUC1 antigen, a membrane-bound glycoprotein, is overexpressed in aberrant or truncated glycosylated forms in various cancers including breast, ovarian, and pancreatic cancers (Du et al., 2020).
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| Host Response |
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| References |
Du et al., 2020: Du JJ, Wang CW, Xu WB, Zhang L, Tang YK, Zhou SH, Gao XF, Yang GF, Guo J. Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses. iScience. 2020; 23(3); 100935. [PubMed: 32146328].
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