Glycoconjugate vaccines: platforms and adjuvants for directed immunity

Central to immune recognition is the glycocalyx, a glycan-rich coat on all cells that plays a crucial role in interactions that enable pathogen detection and activation of immune defenses. Pathogens and cancerous cells often display distinct glycans on their surfaces, making these saccharide antigens prime targets for vaccine development. However, carbohydrates alone generally serve as poor immunogens due to their often weak binding affinities, inability to effectively recruit T cell help, and reliance on adjuvants to iboost immune activation. The introduction of glycoconjugate vaccines, initially involving the covalent coupling of carbohydrate antigens to carrier proteins, marked a pivotal advancement by facilitating neutralizing antibody production against carbohydrate targets. Despite successes in generating glycoconjugate vaccines against certain bacterial diseases, challenges persist in creating effective vaccines against numerous intracellular pathogens and non-communicable diseases such as cancer. In this review, we highlight new developments in conjugate vaccine platforms aim to overcome these limitations by optimizing the display of glycan and T cell epitopes as well as incorporating defined carbohydrate adjuvants to direct tailored immune responses. These advancements promise to improve the effectiveness of carbohydrate-based vaccines and broaden their coverage against a wide range of diseases.