ABSTRACT/PROJECT SUMMARY - Core C (Microneedle Patch Vaccines) The threat of emerging and re-emerging infectious diseases highlights the need for continued improvement of vaccination strategies to enable more effective, sustainable, and equitable global immunization campaigns. As a complementary strategy to the proposed work in the Research Projects (RPs) of this Center, the goal of Core C is to develop, characterize, and validate highly innovative, plug-and-play polyphosphazene (PPZ) adjuvanted dissolvable microneedle patch (MNP) platforms with RP-specific viral antigens to support the proposed research in the RPs of the Center. Development of efficacious, patient-friendly, broadly deployable, and rapidly adaptable PPZ MNP vaccination platforms and validation of their product attributes and immunological properties with the RP-specific antigens against prototype viruses will be of great significance to maximize pandemic preparedness against existing and novel human pathogenic viruses. The Core C of the Center will work seamlessly with Core D and RPs of the Center to bring together the transformative project components, 1) cutaneous immunization, 2) Polyphosphazene (PPZ) adjuvant, and 3) dissolvable MNPs, with the rationally designed antigens that will be developed in RPs against high-priority pathogens to enable the achievement of the overall goals of the Center, as well as to support the translational development of a next-generation immunization strategy. The RP-specific recombinant viral glycoprotein antigens will drive the generation of virus-specific protective immune responses. The PPZ macromolecules will serve as an immunoadjuvant nanoassembly that will provide many immune- potentiating features to complement subunit antigens, such as improved antigen uptake, multivalent antigen presentation, and innate immune stimulation, to rationally augment vaccine-induced immunity. Dissolvable MNPs will enable targeting vaccine components to the highly immunoresponsive skin layers in a reproducible and self- administered manner for efficacious immunization, as well as facilitate the improved vaccine storage, distribution, and coverage due to their thermostability and cost-effectiveness. Together, PPZ MNP vaccines will effectively and safely harness the highly immunoresponsive cutaneous microenvironments to elicit robust, strong, and long- lasting protective immunity against the target pathogen. The Core C will develop and batch release PPZ MNP vaccine platforms with RP-specific antigens based on well-defined quantitative release criteria of their validated physicochemical and immunological properties to enable the development of clinically feasible, highly protective vaccines against several prototype pathogens from multiple viral families in the RPs. Ultimately, these clinically translatable PPZ MNP vaccine platforms are readily adaptable to develop efficacious and broadly deployable vaccines against emerging and re-emerging viruses, including those...