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Vaccine Detail
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Site-78 Azido-Phenylalanine-Incorporated HBc-VLP-MUC1(Tn) Conjugate Vaccine [HBc-N3(78)-MUC1 VLPs] |
| Vaccine Information |
- Vaccine Name: Site-78 Azido-Phenylalanine-Incorporated HBc-VLP-MUC1(Tn) Conjugate Vaccine [HBc-N3(78)-MUC1 VLPs]
- 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 (Cheng et al., 2023)
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Adjuvant:
CFA (Cheng et al., 2023)
- Immunization Route: subcutaneous injection
- Description: A site-specifically modified Hepatitis B core (HBc) virus-like particle (~30nm) vaccine displaying the tumor-associated MUC1 Tn-glycopeptide antigen (SAPDTRPAP with GalNAc moiety on threonine) conjugated via strain-promoted azide-DBCO click chemistry at position 78 (main immune region/spike domain). Position screening revealed only positions 78 and 103 permitted successful VLP assembly, while positions 110 and 122 had poor assembly; conjugation efficiency at position 78 (~87%) was substantially higher than position 103 (~10%) or position 122 (~4%). VLPs demonstrated storage stability at −20°C for at least 1 year with intact structure and retained binding ability. Mice were immunized subcutaneously on days 0, 7, and 14 with CFA. Site-specific modification simultaneously enhanced MUC1 immunogenicity and shielded HBc vector immunogenicity, generating anti-MUC1 IgG titers ~tenfold higher (~10⁴ to ~10⁵) than controls while significantly reducing anti-HBc IgG responses, with anti-MUC1 IgG and MCF7 binding maintained at day 80. VLPs trafficked efficiently to draining lymph nodes enriched in the B cell zone, with 29.93% DCs, 54.21% macrophages, 17.86% migratory DCs, 5.1% resident DCs, 33.94% matured DCs, and 12.98% FDCs among Cy5.5+ cells. At 7 days post-immunization, TFH cells, GC B cells, and plasma cells were significantly elevated. Immune sera mediated strong ADCC (40-50% vs 10-20%), CDC (40-50% vs 70-90% cell viability), and ADCP (~2-3-fold increase) against MUC1-expressing tumor cells in vitro. In a B16-MUC1 melanoma lung metastasis model, pulmonary tumor nodules were reduced to 2-5 versus 50-100+ in controls. In mice with preexisting anti-HBc immunity, HBc-N3(78)-MUC1 VLPs evaded immune clearance, maintained lymph node accumulation, generated robust anti-MUC1 responses, expanded MUC1-specific B cells in spleen and blood, reduced lung metastases, and significantly prolonged overall survival (p<0.001) (Cheng et al., 2023).
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| Host Response |
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| References |
Cheng et al., 2023: Cheng K, Ma N, Liang J, Ma X, Feng Q, Liu G, Xu C, Tang M, Zhang L, Gao X, Xu J, Wang C, Zhu F, Wang X, Li X, Zhao X, Nie G. Site-Specific Modification of Virus-Like Particles for Exogenous Tumor Antigen Display and Minimizing Preexisting Immunity. Small (Weinheim an der Bergstrasse, Germany). 2023; 19(23); e2300125. [PubMed: 36879481].
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