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Covalent Conjugation of Peptide Antigen to Mesoporous Silica Rods to Enhance Cellular Responses
- Source :
- Bioconjugate Chemistry. 29:733-741
- Publication Year :
- 2018
- Publisher :
- American Chemical Society (ACS), 2018.
-
Abstract
- Short peptides are the minimal modality of antigen recognized by cellular immunity and are therefore considered a safe and highly specific source of antigen for vaccination. Nevertheless, successful peptide immunotherapy is limited by the short half-life of peptide antigens in vivo as well as their weak immunogenicity. We recently reported a vaccine strategy based on dendritic cell-recruiting Mesoporous Silica Rod (MSR) scaffolds to enhance T-cell responses against subunit antigen. In this study, we investigated the effect of covalently conjugating peptide antigens to MSRs to increase their retention in the scaffolds. Using both stable thioether and reducible disulfide linkages, peptide conjugation greatly increased peptide loading compared to passive adsorption. In vitro, Bone Marrow derived Dendritic Cells (BMDCs) could present Ovalbumin (OVA)-derived peptides conjugated to MSRs and induce antigen-specific T-cell proliferation. Stable conjugation decreased presentation in vitro while reducible conjugation maintained levels of presentation as high as soluble peptide. Compared to soluble peptide, in vitro, expansion of OT-II T-cells was not affected by adsorption or stable conjugation to MSRs but was enhanced with reversible conjugation to MSRs. Both conjugation schemes increased peptide residence time in MSR scaffolds in vivo compared to standard bolus injections or a simple adsorption method. When MSR scaffolds loaded with GM-CSF and CpG-ODN were injected subcutaneously, recruited dendritic cells could present antigen in situ with the stable conjugation increasing presentation capacity. Overall, this simple conjugation approach could serve as a versatile platform to efficiently incorporate peptide antigens in MSR vaccines and potentiate cellular responses.
- Subjects :
- 0301 basic medicine
Cellular immunity
Ovalbumin
medicine.medical_treatment
Biomedical Engineering
Pharmaceutical Science
Bioengineering
Peptide
Sulfides
03 medical and health sciences
Antigen
medicine
Animals
Disulfides
Antigens
Cells, Cultured
Pharmacology
chemistry.chemical_classification
Immunity, Cellular
Nanotubes
Tissue Scaffolds
biology
Chemistry
Immunogenicity
Organic Chemistry
Dendritic Cells
Immunotherapy
Mesoporous silica
Silicon Dioxide
In vitro
Mice, Inbred C57BL
030104 developmental biology
Biophysics
biology.protein
Female
Peptides
Oxidation-Reduction
Porosity
Biotechnology
Subjects
Details
- ISSN :
- 15204812 and 10431802
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Bioconjugate Chemistry
- Accession number :
- edsair.doi.dedup.....f4dd9f0d3a3d75850581c8f865b0ce03
- Full Text :
- https://doi.org/10.1021/acs.bioconjchem.7b00656