Antibodies, also known as immunoglobulins, are neutralising proteins produced by plasma cells of the mammalian immune system to combat invading pathogens. The specificity of antibodies towards antigenic epitopes is paramount to successful vaccination therapies. This project sets out to enhance antibody specificity by introduction of a molecular address tag (MAT) to vaccines which will ultimately lead to the production of more potent vaccines.
The first type of molecules which we used as MATs is represented by a series of oligo-glycans of various degrees of polymerisation generated from readily available natural polysaccharides. Being attached to a vaccine these MATs will be directed towards a lectin receptor expressed on the surface of dendritic cells provided that this receptors have high affinity to the glycans of chosen type and size. Recognition of MAT ligands by lectin receptors will result in uptake and processing through endocytosis and phagocytosis of the antigenic material also present in the vaccine. Fragments of the antigen are then loaded on to major histocompatibility molecules MHCII triggering TH1 (antibody) immune response.
As prototypes of vaccines with molecular address tags we designed two types of glycan-based glucoconjugates: one based on more conventional protein carrier and another one including liposomes of 100 nm size.
Proposed mode of action of MAT vaccines and liposomes. Picture adopted from Welcome Trust Big Picture.