SialylTn-mAb17-1A Carbohydrate−Protein Conjugate Vaccine: Effect of Coupling Density and Presentation of SialylTn
| Autor: | Geert C. Mudde, Hans Loibner, Ralf Kircheis, Petra Vondru, Renate Ohler, Gottfried Himmler, Andreas Nechansky |
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| Rok vydání: | 2005 |
| Předmět: |
Immunoconjugates
medicine.medical_treatment Biomedical Engineering Pharmaceutical Science Bioengineering Cancer Vaccines Epitope Epitopes Immune system Antigen Antibody Specificity Conjugate vaccine medicine Animals Antigens Tumor-Associated Carbohydrate Pharmacology Vaccines Conjugate Chemistry Organic Chemistry Antibody titer Antibodies Monoclonal Ovine Submaxillary Mucin Macaca mulatta Vaccination Biochemistry Immunoglobulin G Immunologic Memory Adjuvant Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 16:1519-1528 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc050157m |
| Popis: | Carbohydrate antigens resulting from aberrant glycosylation of tumor cells, such as SialylTn, represent attractive targets for cancer vaccination. However, T-cell-independent carbohydrate antigens are poorly immunogenic and fail to induce memory and IgG class switch. Clustered expression patterns of some carbohydrates on the cell surface add further complexity to the design of carbohydrate-based vaccines. We describe here a vaccine consisting of SialylTn carbohydrate epitopes coupled to a highly immunogenic carrier molecule, mAb17-1A, adsorbed on alhydrogel and coformulated with a strong adjuvant, QS-21. The SialylTn-mAb17-1A conjugate vaccine was administered in Rhesus monkeys, and the immune responses against mAb17-1A, SialylTn, ovine submaxillary mucin, and tumor cells were analyzed. The data demonstrate that the density of carbohydrate epitopes on the carrier is an essential parameter for induction of anti-carbohydrate specific memory IgG immune responses. Furthermore, the influence of different types of presentation of SialylTn (monomeric vs trimers vs clustered via a branched polyethylenimine linker) on antibody titers and specificity was studied. High-density coupling of SialylTn epitopes to mAb17-1A induced the strongest immune response against synthetic SialylTn and showed also the highest reactivity against natural targets, such as OSM and tumor cells. |
| Databáze: | OpenAIRE |
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