"Click" Chemistry for the Assembly of Entirely Carbohydrate-based Vaccines

Abstract

The immunogenicity of conjugate vaccines is affected by the type of linker used. Due to its ease of synthesis, the "click" triazole linker is now widely used, but its impact on vaccine immunogenicity remains understudied, and current findings are contradictory, due to the difficulty of isolating the linker's effect. To do this, we have synthesized two vaccines targeting the Thomsen-nouveau (Tn) carbohydrate cancer antigen, using a zwitterionic polysaccharide carrier, PS A1, with either a linker-free or triazole-based conjugation strategy through an oxime bond. Evaluation of the triazole conjugate in C57BL/6 mice shows a 30% decrease in antibodies targeting Tn and conversely, a large immune response towards the triazole. Despite this moderate loss of antibodies, complement-dependent cytotoxicity is unaffected. Overall, the application of "click" chemistry allows for facile conjugation of amino-and azido-bearing antigens to PS A1, allowing for expanded antigen conjugation strategies as potential vaccine candidates with limited impact on clinical outcomes.