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Vaccine Detail
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MUC1-KLH/DHBcAg conjugate vaccine |
| Vaccine Information |
- Vaccine Name: MUC1-KLH/DHBcAg conjugate vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 2 MUC1 VNTRs, 40aa (APPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGST) (Gathuru et al., 2005)
- Immunization Route: subcutaneous injection
- Description: A conjugate vaccine containing a 40-mer MUC1 peptide (APPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGST) covalently conjugated via MBS linker to either keyhole limpet hemocyanin (KLH) at a molar ratio of 2505:1 or Duck Hepatitis B core antigen (DHBcAg) particles at a molar ratio of 505:1 (MUC1:carrier), formulated with 200 µg saponin adjuvant GPI-0100. DHBcAg is a 262 amino acid monomer (~25 kDa) that self-assembles into ~240-mer particles of approximately 6.4 × 10⁶ Da, readily purified to homogeneity. Administered subcutaneously in CBF1 mice in two sequential rounds of three weekly immunizations (3 µg MUC1 per dose), separated by a 6-week interval. No detectable anti-MUC1 IgG or IgM antibodies were observed prior to vaccination. After the first three vaccinations, MUC1-DHBcAg achieved median IgG ELISA titers of 1/51,200 and IgM of 1/1,600, exceeding MUC1-KLH (IgG 1/12,800; IgM 1/3,200). During the 6-week interval before boosting, IgG and IgM titers fell 2–8 fold in all groups (pre-4th bleed: MUC1-KLH IgG 1/6,400; MUC1-DHBcAg IgG 1/6,400–1/12,800). After three booster immunizations with the same carrier, both groups reached IgG titers of 1/6,553,600 and IgM titers of 1/51,200, while groups switched to the alternate carrier achieved significantly lower IgG titers of 1/51,200–1/409,600 and IgM titers of 1/1,600 (p<0.05). Flow cytometry on MUC1-positive MCF7 human breast cancer cells showed strong IgG surface reactivity post-prime: MUC1-DHBcAg 98% positive cells (MFI 56) and MUC1-KLH 89% (MFI 29), maintained at 81% (MFI 23) and 86% (MFI 30) respectively post-boost when the same carrier was used. IgM surface reactivity declined across all groups post-boost, ranging 8–32% regardless of carrier sequence. Complement-dependent cytotoxicity against MCF7 cells was not induced in either group despite high ELISA and FACS titers (MUC1-KLH 3.9%; MUC1-DHBcAg 1.6%). These results demonstrate DHBcAg is at least as potent a carrier as KLH, and that maintaining a consistent carrier throughout the full immunization course produces significantly higher antibody titers than switching carriers mid-schedule (Gathuru et al., 2005).
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| Host Response |
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| References |
Gathuru et al., 2005: Gathuru JK, Koide F, Ragupathi G, Adams JL, Kerns RT, Coleman TP, Livingston PO. Identification of DHBcAg as a potent carrier protein comparable to KLH for augmenting MUC1 antigenicity. Vaccine. 2005; 23(39); 4727-4733. [PubMed: 15978705].
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