Rapid, single-dose coronavirus vaccines via DNA-launched nanoparticles and genetic adjuvants for durable anti-coronavirus immunity

Project 2 Summary There is an urgent need to develop vaccines which induce robust and lasting immunity against current and emerging pathogenic coronaviruses (CoVs). These vaccines must also be immunogenic in elderly patients as they are at increased risk of severe coronavirus disease. Many novel CoVs with pandemic potential remain poised for human transmission, and elderly patients are at increased risk of morbidity and mortality, emphasizing the need for predesigned next-generation vaccination platforms with robust preclinical data indicating increased potency and breadth against structurally related CoVs. This team has recently described the design and study of in vivo self-assembling nanoparticles for generation of more potent and rapid humoral and cellular responses in both the HIV and influenza models. Here we propose to apply this proof-of-principal immunization design strategy in the CoV model system. Under this program we will develop and characterize a series of structurally tuned, genetically adjuvanted, synthetic DNA (synDNA)-launched nanoparticle (DLNP) immunogens based on our recent designs for the SARS-CoV-2 spike antigen. We previously reported on the ability of DLNPs to induce robust immunity compared to traditional synDNA and protein-in-adjuvant vaccine formulations. In collaboration with Project 1 we will evaluate the capacity of these immunogens to foster potent and durable immunity against SARS-CoV-2 and related viruses. In summary, the goal of this project is to define the effect of manipulating epitope valency, size, and adjuvant environment on self-assembling DLNP vaccine on the magnitude, functionality, and half-life of responses in young and aged mouse models. These experiments will provide mechanistic insight into the effects of epitope manipulation on vaccine-induced responses and define the parameters which induce robust and durable anti-CoV immunity.