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Vaccine Detail
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Oxidized mannan-MUC1 fusion protein (M-FP) vaccine ± GM-CSF+IL-7 |
| Vaccine Information |
- Vaccine Name: Oxidized mannan-MUC1 fusion protein (M-FP) vaccine ± GM-CSF+IL-7
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR, 20aa (McKenzie et al., 1998)
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Adjuvant:
Oxidized mannan (McKenzie et al., 1998)
- Immunization Route: Intraperitoneal injection (i.p.)
- Description: Oxidised mannan-MUC1 fusion protein (MFP) conjugate vaccine administered to nine different mouse strains generated robust MHC Class I-restricted CD8+ CTL responses with a CTLp frequency of approximately 1/8,000 after three injections, alongside CD4+ T cell-mediated DTH reactions and weak antibody production, consistent with a T1-type immune profile, with production of IFN-γ, IL-2 and IL-12 and absence of IL-4. In tumour challenge experiments, mice previously susceptible to 5×10⁶ tumour cells became resistant to 5×10⁷ MUC1+ tumour cells following oxidised MFP immunisation. By contrast, reductive conjugation of mannan-MUC1 gave a CTLp frequency of only 1/85,000 with strong antibody production and IL-4 secretion characteristic of a T2 response; similarly, MUC1 fusion protein alone gave 1/85,000 with T2 responses, and MUC1 peptide conjugated to KLH or diphtheria toxoid gave 1/150,000 with strong antibody and negligible CTL. MHC restriction was confirmed using Class I knockout mice, H-2 mutants and recombinants, with MUC1 epitopes mapped to Kᵇ, Dᵇ, Lᵈ, Dᵈ and Kᵏ alleles. Co-administration of exogenous cytokines after a single immunisation modulated CTLp frequency from a baseline of 1/80,000: GMCSF+IL-7 most potently enhanced responses as the strongest combination (1/18,000), followed by IL-12 (1/19,000), IL-2 (1/49,000) and IFN-γ (1/74,000), while IL-4 suppressed CTL induction (1/225,000). Simultaneous administration of both oxidised and reduced MFP to separate sites successfully induced concurrent T1 and T2 responses, demonstrating the potential to generate both cellular and humoral immunity within a single vaccination regimen. The oxidised mannan conjugation platform was additionally validated with ovalbumin (SIINFEKL), listeria-derived peptides, HPV E7 papilloma peptides and other MUC1 peptides, all generating measurable CTL responses (McKenzie et al., 1998).
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| Host Response |
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| References |
McKenzie et al., 1998: McKenzie IF, Apostolopoulos V, Lees C, Xing PX, Lofthouse S, Osinski C, Popovski V, Acres B, Pietersz G. Oxidised mannan antigen conjugates preferentially stimulate T1 type immune responses. Veterinary immunology and immunopathology. 1998; 63(1-2); 185-190. [PubMed: 9656453].
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