Project Summary/Abstract – Overall: The UCI Vaccines for Pandemic Preparedness Center (VPPC) The Mission: "To contribute to human health and well-being by developing agile, safe, effective and accessible vaccines that protect the vulnerable against future pathogens of pandemic importance and by educating the next generation of vaccine scientists that will tackle such challenges.” Joshua Lederberg envisioned the world as a battlefield between microbes and man, famously saying, “The future of humanity and microbes likely will unfold as episodes of a suspense thriller that could be titled Our Wits Versus Their Genes” (Lederberg, 2000). Although the genes of the microbial world have been evolving much longer than our wits, we have come up with efficient ways to respond to infectious diseases, but regrettably evolving microorganisms keep managing to challenge and outsmart us. The latest COVID episode in this series sensitized the world again to the importance of learning from the outbreak experience and challenges us to better prepare for the next one. The 100 Days Mission (100DM), endorsed by government and non-government organizations worldwide is a proposed response to the next “Disease X” by making safe, and effective vaccines available within 100 days of the pathogen’s identification. Achieving that goal could defuse the threat of a pathogen with pandemic potential. The International Pandemic Preparedness Secretariate (IPPS), the Coalition for Epidemic Preparedness Innovations (CEPI), the HHS Administration for Strategic Preparedness and Response (ASPR Next) and the NIH/NIAID have embraced the concept of studying prototype pathogens as a critical element of preparedness. By developing vaccines on rapid-response platforms against examples of a given viral genus or family, researchers can address scientific challenges characteristic of that family in advance, providing an important head start on developing vaccines against related threats. Universal programmable vaccine platforms that can be rapidly employed against broad virus families can be evaluated in clinical trials to provide confidence in their safety, and manufacturing, and regulatory considerations can be managed ahead of the next outbreak. The UC Irvine Vaccines for Pandemic Preparedness Center (VPPC) aims to conduct basic and translational research to develop vaccines against prototype members of the Bunyavirus, Paramyxovirus and Picornavirus families with demonstrated immunogenicity and efficacy in animal models. Two universal, programmable, rapid response vaccine platforms will be characterized and compared in this study: the i) Adjuvanted Recombinant Protein (ARP) Vaccine, and ii) mRNA/Lipid Nanoparticle (LNP) Vaccine. Such prototype vaccines will need to be tested in advance, at a minimum, for clinical safety and immunogenicity, and efficacy where possible, so that emerging viruses in the same family can be rapidly and safely deployed. Gathering such data and experience will build confidence in these rapid response platforms and inform regulators as they make decisions about the emergency authorization of vaccines against related pathogens.

Narrative - Overall Vaccines are a demonstrably effective tool for blunting the global health consequences of emerging infectious diseases like COVID; however, they must be delivered quickly to limit outbreak spread and reduce human mortality. Here, two different programmable vaccine platforms primed for quick deployment will be compared and characterized. The knowledge and technology gained from this project will enable a rapid and effective response to the next pandemic.