Characterization and optimization of single dose, thermostable and durable vaccine platform towards increased clinical acceptance - SUMMARY/ABSTRACT Broadening the spectrum of vaccine platforms that confer protective, durable and broad immunogenicity is important for pandemic preparedness. Here, we aim to create essential preclinical data to characterize a novel genetic vaccine platform called PARVAX to increase its clinical acceptance. Our previous studies show that a single dose of PARVAX candidates for COVID-19 elicits sustained humoral immunity, near-sterilizing upper and lower airway protection from a SARS-CoV-2 challenge, and potent and durable cellular responses. These qualities combined with established commercial and low-cost manufacturing processes, make this platform imminently feasible, scalable and affordable for vaccine applications. In this proposal, we will investigate the mechanism behind the potency and durability of PARVAX, which we hypothesize is correlated with antigen expression kinetics (Aim 1). We also use rational engineering approaches to enhance the potency of the PARVAX platform, which will enhance safety and applicability for other pathogens (Aim 2). Finally, we propose to generate proof of the potency of PARVAX as a vaccine platform beyond COVID-19 by exploring the serum and mucosal immunity and protection from influenza viruses in two preclinical models of influenza infection (Aim 3). The proposed work is highly relevant for pandemic preparedness, since it will enable the rapid design of new and preclinically derisked PARVAX candidates for existing and future pathogens, and has the potential to provide clarity on the means to improve the durability, breadth and mucosal immunity of other platforms.
