Vaccines offer a treatment opportunity based upon successful genetic and protein antigen delivery to specific immune cell modulators. Driving the process is the vector chosen for gene and protein cargo packaging and subsequent delivery to antigen presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this application, we present a novel hybrid delivery vector containing biological and biomaterial components. Each component was chosen to separately design and engineer delivery in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial (poly(beta-amino ester))-coated outer surface allow the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC antigen delivery which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combines and synergizes normally disparate vector properties and tools, resulting in increased delivery capabilities beyond individual vector components. Furthermore, the same design features of the hybrid vector allow for improved APC cellular viability in vitro and the potential for tailored APC cellular responses in vivo. In summary, the flexibility, diversity, and potential of the hybrid desgn were developed as a platform for multivariate engineering at the vector and cellular scales for new applications in immunotherapy. The proposed work will test the capabilities of the hybrid vector in the context of antigen delivery using in vivo mouse models. Specifically, three different antigens (Ova [a model antigen], PspA [an antigen implicated in Streptococcus pneumoniae infection], and HER2/neu [a recognized breast cancer biomarker]) will be tested using the hybrid vector technology with the goal in each case to elicit safe, potent, and specific immune responses. Success will build upon the current data supporting the delivery potential of the hybrid vector and preface the technology for later comprehensive immunization plans utilizing the antigens introduced above (and many others) in the context of infectious disease and cancer vaccination.
The proposed research is designed to test potent and specific immune responses as a function of a new hybrid biological-biomaterial antigen delivery device. Long-term, success is expected to translate to new vaccines that provide enhanced production and engineering capabilities.
