Ionic Liquid Adjuvants for Infectious Disease Vaccines

Abstract

Vaccination is a strategy that has been utilized for centuries for the prevention of infectious diseases globally. Adjuvants can be utilized in vaccines to enhance the resulting immune response as well as specify it to the needs of the pathogen for complete protection. Despite the potential of adjuvants to improve vaccination, there has been slow development in the field, resulting in a small material landscape. There is a need for more adjuvants, specifically those that can result in strong humoral and cellular immune responses. Ionic liquids have many enticing material properties for use as adjuvants including their manufacturability and tunability. In this thesis, I develop multiple ionic liquid candidates by varying the anion hydrophobicity and screen them for vaccine adjuvancy. By screening the ionic liquid candidates through in vitro immune cell activation, antigen stability, and in vivo immune responses, an ionic liquid comprised of choline and sorbic acid, ChoSorb, was found that produced a balanced antigen- specific immune responses. ChoSorb was then explored mechanistically, firstly revealing its low dose potency and autonomous efficacy when delivered separately from the antigen. The innate immune response to ChoSorb was evaluated as well as the cell death pathways initiated in the injection site for heightened understanding of ChoSorb’s initial impact on the body upon vaccination. Finally, the clinical vaccine, FluBlok, was adjuvanted with ChoSorb and delivered through two routes of administration to assess the breadth of the adjuvant: displaying enhanced and balanced immune responses upon adjuvantation. Altogether, this work introduces ionic liquids as robust adjuvants for use in infectious disease vaccines and reveals the potential mechanism and range of the first balanced ionic liquid adjuvant, ChoSorb.