Immunological Evaluation of Conformationally Constrained Tn and sTn Analogues

<jats:p>Conjugate vaccines, targeting tumor-associated carbohydrate antigens (TACAs), have met clinical challenges that have been attributed to heterogeneous TACA presentation on the surface of tumors cells and low vaccine immunogenicity. A promising strategy to improve immunogenicity is to lock the target antigen in its biologically active conformation, improving presentation in antigen presenting cells. In this study, Tn-Thr and sTn-Thr conformationally restricted TACA mimics were conjugated to the low immune interfering, high-loading, entirely carbohydrate vaccine carrier, PS A1, followed by in vivo evaluation. According to ELISA and FACS data analysis of raised antibodies in C57BL/6J mice, a Tn-Thr-PS A1 mimic conjugate proved to be better in comparison to a Tn-PS A1 control. However, the sTn-Thr-PS A1 mimic conjugate did not benefit from Tn restricted conformation, hinting at a less prominent role of the core D-GalNAc moiety in immune recognition.</jats:p>