Development of potential new vaccine adjuvants inspired by Lipid A structure of Bacteroides fragilis

Adjuvants are components of vaccine formulations widely used to enhance their overall efficacy, providing an enhancement in the response towards antigens and allowing for the use of smaller doses of vaccine active ingredient[i]. Up to date, only few adjuvants are licensed and, only recently, their mechanism of action started to be understood. Hence, new efforts are needed for the research of novel chemical entities to be developed as adjuvants. Bacteroides fragilis is a Gram-negative bacterium belonging to the human gastrointestinal microbiota, involved in the homeostasis of host immune system. Recently, new Lipid A moieties of this bacterium have been isolated, showing promising immunomodulatory activities[ii]. This feature, coupled with their probable low toxicity, makes them interesting candidates for the development of new vaccine adjuvants. In fact, some low toxicity Lipid A-based compounds can be used in vaccine formulations, as demonstrated by the authorization for the clinical use of “Monophosphoryl Lipid A”, the first TLR-agonist vaccine adjuvant[iii]. The glycolipid mixture isolated from B. fragilis is only partially characterized and their exact structures is still not completely established. In this context, our project is focused on the chemical synthesis of a small library of Lipid A structures (Figure 1), based on the available information, with the aim to define and clarify their chemical structures and their immunological properties, as well as to investigate their potential application as vaccine adjuvants.