University of Galway researchers have developed a modular approach to vaccine synthesis, potentially enabling production of a new cancer vaccine prototype.
The study, published in the Journal of the American Chemical Society, is a collaboration involving a number
of laboratories in Ireland, Germany, Sweden, the Netherlands, Spain and the US. The research paper describes a novel approach and has implications for vaccine design.
The vaccine contains three different components, which can be assembled like Lego blocks, said the researchers. The first is a targeting component, a glycocluster, to selectively deliver and increase uptake of the vaccine into the relevant cells of the immune system. The second component is a T-helper epitope in order to generate long-term immunity. The third component is a cancer T-antigen containing molecule (MUC-1), in order to stimulate the immune system to generate immunity against cancer- associated antigens found on breast tumour cell surfaces.
The incorporation of the glycocluster has led to a much-improved immune response to the vaccine, the researchers commented. The glycocluster molecule is comprised of multiple sugars and has a high affinity for a receptor (macrophage galactose C-type lectin) on certain immune cells (dendritic cells). The vaccine is about 10 times ‘stickier’ when it has the glycocluster than when it is absent, which explains its greater uptake into the immune cells and increased efficacy observed for the vaccine prototype, said the researchers.
The modular or ‘Lego-block’ approach means that other types of glycoclusters targeting other immune cell lectins or T-helper epitopes or tumour antigens could be built and studied in a systematic manner and thus contribute to the field of vaccine design.
The study was primarily carried out by Dr Adele Gabba while she was a PhD student at University of Galway, under the supervision of Prof Paul Murphy, and subsequently as a postdoctoral fellow in the laboratory of Prof Pol Besenius at the Johannes Gutenberg University of Mainz, Germany. During the PhD study, Adele obtained an EMBO travel award which enabled travel to the laboratory of Prof Ulrika Westerlind at Umea University in Sweden, where vaccine constructs used in the study were prepared. The research was performed in a collaboration with laboratories also in Amsterdam, Boston and in Spain.
Prof Murphy, Established Professor of Chemistry at University of Galway and SFI Investigator, said: “I am hugely in debt to all the collaborators for all their contributions, and especially grateful to Dr Adele Gabba for the persistence she showed throughout, which was the key to the success of this research, spanning her PhD study and a subsequent period as a postdoctoral researcher in Mainz.
“Glycoclusters, after many years of study, are beginning to show applications that benefit health and industry. It may even be possible to use the modular approach incorporating glycoclusters to design vaccines for infectious diseases caused by bacteria or viruses or for the targeted delivery of biopharmaceuticals or small molecule drugs to where they are needed. Importantly, no adverse effects were observed of the prototype during the study, while the efficacy was improved.”