Project 463759

Novel adjuvants for vaccines are highly desirable, especially if they can be synthesized instead of being derived from natural products. Additionally, the adjuvant should be capable of inducing a greater and more desired immune response - such as directing the response towards a Th1-like response. TriAdj is a fully synthetic adjuvant that directs the immune response towards a Th1-like response and moreover, is capable of providing protection in both the upper and lower respiratory tract in multiple animal models of multiple pathogens. TriAdj has proven effective in ferret, hamster and African green monkey models of SARS-CoV-2 and an alpaca model of MERS-CoV. It will be used in a phase 1 clinical trial starting in fall 2021. Here we propose to optimize the order and state in which the 4 components a TriAdj containing vaccine are assembled to move the development of TriAdj, to a higher level of tech readiness. TriAdj is a three component adjuvant that when mixed with an antigen, in this case the S1 protein from SARS-CoV-2 for an antigen/adjuvant complex that is more effective at inducing an immune response than when it is not in this complex. Our current formulation requires three individual vials, which is not optimal and therefore we will determine whether and how best to formulate this vaccine so that it can be used in a conventional two or single vial manner. To do this, we will assess various orders of addition and state (liquid/dry) to streamline this product. To characterize the structure of the adjuvant/antigen complex we will also perform state of the art imaging, which will help link the structural characterization of the vaccine to its performance. Further development of TriAdj will provide a tool to be used against emerging Disease X-like pathogens.