Translational Development of a Microneedle Patch SARS-CoV-2 Ferritin Nanoparticle Vaccine

Emerging and re-emerging infectious pathogens are a major public health concern with significant impact on civilian population and military personnel. The unparalleled threat of infectious pathogens has been further underscored by the Coronavirus disease 2019 (COVID-19) pandemic that has had tremendous impact on global health and the global economy and is an ongoing threat to public health due to emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. Most importantly, the repeated emergence of novel infectious diseases or new strains of existing viruses seems inevitable, highlighting the need for continued improvement of vaccination strategies to enable effective, sustainable, and equitable mass vaccination campaigns against infectious pathogens, including emerging coronaviruses. The overarching goal of this project to develop a next-generation vaccination strategy using readily translatable vaccine antigen, adjuvant, and delivery platforms, which can be rapidly developed based on sequence information alone, for safer, more effective, and more widespread immunization against emerging and re-emerging infectious pathogens. In this project, we propose to complete the translational development of a novel skin-targeted SARS-CoV-2 vaccine that will be broadly effective against emerging coronaviruses and to submit an Investigational New Drug (IND) application toward clinical development of this novel vaccine. Our unique SARS-CoV-2 vaccine will be enabled by a novel antigen platform, SARS-CoV-2 Spike protein Ferritin Nanoparticle (SpFN), an emerging liposomal adjuvant (ALFQ), and an innovative skin-targeted vaccine delivery technology, dissolvable microneedle patches (MnPs). Specifically, we will manufacture a broadly effective and widely deployable SARS-CoV-2 vaccine by incorporating SpFN and ALFQ developed by investigators at the Walter Reed Army Institute of Research (WRAIR) into a dissolvable MnP platform developed by investigators at the University of Pittsburgh (UPITT), as well as complete the preclinical evaluation of the safety, immunogenicity, protection efficacy, and translational correlates of this dissolvable MnP-based vaccine through animal studies and experiments using living human skin explants. The outcome of this project will be a next-generation immunization approach, enabled by transformative plug-and-play vaccination platforms, to facilitate significantly improved civilian and military immunization programs against SARS-CoV-2 variants and to address the long-term threat of emerging coronaviruses. These clinically feasible, plug-and-play platforms will be readily adaptable to develop efficacious and safe vaccination strategies against other existing and novel pathogens. Together, this project will directly address the Fiscal Year 2022 (FY22) Portfolio Strategic Goal of developing and optimizing vaccine strategies, platforms, or compounds under the FY22 Peer Reviewed Medical Research Program (PRMRP) Topic Area of viral diseases for the FY22 Portfolio of infectious diseases. The skin is a more potent vaccination target than traditional vaccination routes, including subcutaneous tissue and muscle, since it contains a more immunoresponsive microenvironment than the latter tissues. Self-assembling protein nanoparticle antigen, such as SpFN, offer a next-generation vaccine technology that provides multivalent antigen presentation and enables better recognition and presentation of antigen by the immune system compared to soluble monovalent antigens. ALFQ is an emerging immune potentiator that efficiently and safely links the innate and adaptive immune responses to enhance both humoral and cellular immune responses elicited by subunit protein vaccines. Dissolvable MnPs stand out as a promising vaccine delivery technology that can reproducibly target vaccine components to the immunologically rich milieu of the skin and offers a needle-free, thermostable, self-administered, and widely deployable vaccine delivery platform. The central hypothesis of this project is that skin immunization via dissolvable MnP delivery of SpFN adjuvanted with ALFQ will enable a broadly effective and widely deployable vaccination strategy against emerging coronaviruses. Previous clinical approval of the SpFN + ALFQ intramuscular vaccine (WRAIR, NCT04784767) and our dissolvable MnPs (UPITT, NCT02192021) strongly supports our hypothesis and the translational feasibility of our novel skin-targeted SARS-CoV-2 vaccine that will be developed in the form of ALFQ and SpFN loaded dissolvable MnPs. Collectively, this project will synergistically combine clinically feasible SpFN, ALFQ, and MnPs as a broadly effective, safe, needle-free, thermostable, low-cost, self-administered, and widely deployable next-generation vaccination platform that will more effectively address the long-term threat of emerging coronaviruses and offer a set of robust platforms for better pandemic preparedness. Comprehensive translational development of these plug-and-play vaccination platforms (Ferritin nanoparticle vaccine, ALFQ, and MnPs) for a next-generation SARS-CoV-2 vaccine, will enable clinical development for more effective civilian and military immunization programs and will facilitate their deployment against other infectious pathogens ensuring sustainable global pandemic preparedness in the future. Less