Vaccine Adjuvants · Chemical Synthesis, Immunologic Evaluation and Conformational Analysis by NMR Spectroscopy of Complex Glycoconjugate Adjuvants for Anti-Cancer and Anti-Viral Vaccine Therapies

The development of therapeutic vaccines often includes the use of synthetic small molecule antigen constructs to elicit immune response. However, many subunit antigen vaccines are less immunogenic than those employing attenuated microorganisms. As a result, they often require co-administration with an adjuvant or immunostimulating complex, a substance that is itself not necessarily immunogenic but functions in concert with the antigen to enhance/prolong immune response. Whereas the design of subunit antigen constructs has played an influential role in the development of clinically viable vaccine therapies, efficacy modulation of vaccines through the design and chemical synthesis of distinct molecular adjuvants has been comparatively less common given the structural complexity of these substances. With the aid of several chemical glycosylation methodologies developed in Professor Gin laboratories, the first synthesis and structure verification of several complex triterpene saponins have been achieved. Through collaborations with immunologists and clinicians, current efforts are also devoted to the generation of designed structural analogs for the development of more powerful and stable adjuvants for both anti-cancer and anti-viral therapeutic vaccines. At a final stage, recent progress made in Professor Jiménez-Barbero group on the application of NMR methods to study the structural and recognition properties of carbohydrates will allow us to gain insights into the conformational behavior and the immunostimulating activity of these newly synthesized adjuvants. Thus, we will carry out advanced NMR experiments to assess the conformational features and aggregation properties of these compounds . As a consequence, we are in a unique position to conduct systematic structure-activity investigations on this class of natural product with the goal of unraveling its as yet unknown mechanism of immunostimulatory activity.