SialylTn-mAb17-1A Carbohydrate-Protein Conjugate Vaccine: Effect of Coupling Density and Presentation of SialylTn

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• 作者：Ralf Kircheis ; Petra Vondru ; Andreas Nechansky ; Renate Ohler ; Hans Loibner ; Gottfried Himmler ; and Geert C. Mudde
• 刊名：Bioconjugate Chemistry
• 出版年：2005
• 出版时间：November 2005
• 年：2005
• 卷：16
• 期：6
• 页码：1519 - 1528
• 全文大小：867K
• 年卷期：v.16,no.6(November 2005)
• ISSN：1520-4812

文摘

Carbohydrate antigens resulting from aberrant glycosylation of tumor cells, such as SialylTn, representattractive targets for cancer vaccination. However, T-cell-independent carbohydrate antigens are poorlyimmunogenic and fail to induce memory and IgG class switch. Clustered expression patterns of somecarbohydrates 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 highlyimmunogenic carrier molecule, mAb17-1A, adsorbed on alhydrogel and coformulated with a strongadjuvant, 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 cellswere analyzed. The data demonstrate that the density of carbohydrate epitopes on the carrier is anessential parameter for induction of anti-carbohydrate specific memory IgG immune responses.Furthermore, the influence of different types of presentation of SialylTn (monomeric vs trimers vsclustered 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 againstsynthetic SialylTn and showed also the highest reactivity against natural targets, such as OSM andtumor cells.