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Vaccine Detail
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AcDEX-(imine) Nanoparticle Vaccine Conjugated to MUC1 Epitopes (TSAPDTRPAP/SAPDNRPAL) and R837 |
| Vaccine Information |
- Vaccine Name: AcDEX-(imine) Nanoparticle Vaccine Conjugated to MUC1 Epitopes (TSAPDTRPAP/SAPDNRPAL) and R837
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (TSAPDTRPAP; SAPDNRPAL); SARS-CoV-2 Spike protein; ORF1ab polyprotein; Nucleocapsid protein (Gao et al., 2021)
- Immunization Route: subcutaneous injection
- Description: An acid-responsive polymeric nanoparticle conjugate vaccine composed of partially oxidized acetalated dextran nanoparticles (Ox-AcDEX NPs, ~100 nm diameter) covalently conjugated with synthetic CTL peptide epitopes and TLR-7 agonist R837 via pH-labile imine (Schiff-base) bonds, enabling acid-responsive endolysosomal antigen release and MHC-I cross-presentation superior to free peptide and non-covalently loaded controls. For anticancer applications, MUC1 epitopes Mp1 (TSAPDTRPAP, VNTR region) and Mp2 (SAPDNRPAL, non-VNTR, higher H-2K? binding affinity) were conjugated with R837. Despite higher MHC-I binding affinity of Mp2, Mp1 was the superior protective epitope, demonstrating binding affinity does not predict protective capacity. Free peptides were ineffective or minimally protective, requiring NP delivery for robust H-2K?-restricted CD8? CTL responses detectable in spleen and lymph nodes beyond 120 days. In B16-MUC1 tumor challenge, Mp1 NPs significantly reduced tumor growth (p<0.01 to p<0.001), with the Mp1+Mp2 combination providing strongest protection. For anti-SARS-CoV-2 applications, screening of 11 epitopes identified four highly protective CTL epitopes: Sp1 (SYGFQPTNGVGYQPY) and Sp2 (SIIAYTMSL) from spike protein effectively killed S protein-pulsed and pseudovirus-infected target cells; Sp9 (NALAYYNTT, ORF1ab) achieved ~57% target cell lysis; Sp11 (LALLLLDRL) from nucleocapsid protein effectively killed N protein-pulsed target cells. Vaccination with Sp1 and Sp2 NPs upregulated MHC-I, CD86, CD8, CD4 and CD8?CD45RO? memory T cells with no detectable TNF-? or IFN-?, confirming robust CTL induction without cytokine storm (Gao et al., 2021).
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| Host Response |
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| References |
Gao et al., 2021: Gao Y, Zhao Q, Dong H, Xiao M, Huang X, Wu X. Developing Acid-Responsive Glyco-Nanoplatform Based Vaccines for Enhanced Cytotoxic T-lymphocyte Responses Against Cancer and SARS-CoV-2. Advanced functional materials. 2021; 31(41); 2105059. [PubMed: 34512228].
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