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Vaccine Detail
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Qβ-MUC1 SAPDT(Tn)RPAP Conjugate Vaccine |
| Vaccine Information |
- Vaccine Name: Qβ-MUC1 SAPDT(Tn)RPAP Conjugate Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 9-mer MUC1 (SAPDTRPAP), Tn at T5 (Wu et al., 2018)
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Adjuvant:
MPLA; CFA/IFA (Wu et al., 2018)
- Immunization Route: subcutaneous injection
- Description: A synthetic MUC1 glycononapeptide (SAPDT*RPAP, where * denotes GalNAc/Tn O-glycosylation at threonine) conjugated via a flexible alkyl amide linker to bacteriophage Qβ virus-like particle carrier, with an average of 270 glycopeptide copies per Qβ capsid. First generation Qβ-MUC1 constructs bearing the full tandem repeat elicited strong anti-MUC1 IgG responses in wild-type mice but less than 3% of equivalent tumor cell binding in immunotolerant MUC1.Tg mice despite similar total IgG titers, mirroring clinical trial failures. Peptide array epitope profiling revealed that HGVTSAPD and APGSTAPP regions were immunodominant but nonprotective, showing comparable antibody binding levels in both wild-type and MUC1.Tg mice, while SAPDTRPAP showed significantly stronger binding in wild-type versus MUC1.Tg mice, identifying it as the critical protective epitope. These nonprotective epitopes may compete with protective epitope induction through antigen competition, steric blocking of adjacent epitopes, or outcompeting low-frequency protective B cells for limited helper T cell signals in the tolerant environment. Removing these nonprotective epitopes and focusing the vaccine on the shortened SAPDT*RPAP glycopeptide optimized protective immune responses. GalNAc glycosylation of the threonine residue renders the epitope more immunogenic by making it appear more "foreign" to the immune system through glycan-induced conformational changes. Qβ provides organized multivalent antigen display, endogenous CD4+ T helper epitopes, and encapsulated nucleic acid for immune potentiation. Administered subcutaneously with CFA/IFA or MPLA as adjuvant in MUC1.Tg mice, Qβ-MUC1 43 induced anti-MUC1 IgG antibody titers approximately 2.7-fold higher than KLH-MUC1 (123,800 vs. 45,000) and approximately 2-fold stronger tumor cell binding against B16-MUC1 melanoma and MCF-7 breast cancer cells with negligible binding to normal MCF-10A cells. Glycopeptide microarray profiling confirmed selective recognition of glycopeptides bearing Tn in the PDT*R region with no cross-reactivity to MUC5 or other glycoproteins. Post-immune sera demonstrated tumoricidal activity via CDC against B16-MUC1 and MCF-7 cells and ADCC using NK and LAK effector cells. In a lung metastasis model, vaccination significantly reduced pulmonary tumor foci versus Qβ control (p=0.0006) and KLH-MUC1 (p=0.037). In a subcutaneous solid tumor model combined with anti-PD-1 checkpoint blockade, Qβ-MUC1 43 significantly reduced tumor volume versus Qβ control (p<0.05). Post-immune sera showed high selectivity for human breast cancer tissues over normal adjacent breast tissues on tissue microarrays (Wu et al., 2018).
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| Host Response |
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| References |
Wu et al., 2018: Wu X, Yin Z, McKay C, Pett C, Yu J, Schorlemer M, Gohl T, Sungsuwan S, Ramadan S, Baniel C, Allmon A, Das R, Westerlind U, Finn MG, Huang X. Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice. Journal of the American Chemical Society. 2018; 140(48); 16596-16609. [PubMed: 30398345].
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