We plan to develop a novel family of vaccine adjuvants through bioengineering a microbial glycolipid. This polymeric material is generated as a secreted product from the bacterium, Acinetobacter calcoaceticus and in preliminary studies demonstrates exceptional adjuvant activity. To further explore this application, we plan to correlate structural features of the polymer with macrophage response in vitro and antibody response in vivo to a series of these analogs. The Phase I studies will determine if the nature of the macrophage response is structure-specific, and if so, which structural features are most important. These features will then be assessed in vivo in a murine Lyme vaccine model. To accomplish this goal we will generate a family of structural analogs using methods we have recently developed, and then characterize these analogs for selectivity of responses of macrophages in terms of cytokine release followed by antibody response in vivo. The outcome of Phase I will be a selection of the best few candidate structures to move forward into more detailed in vivo testing in Phase II.
The development of a family of structurally related vaccine adjuvants is of considerable relevance for establishing structure-property relations and tailored therapeutics.
