The significance of this grant is that it will provide for panbetaCoV vaccines (universal vaccines) for future epidemics that can be immediately available at the onset of a betaCoV pandemic, avoiding much of the human tragedy and social disruption caused by a pandemic.
The overall specific aims of the grant (P01) are:
Aim 1. Develop and characterize immunogenicity of PanbetaCoV Sarbecovirus (Group 2b) vaccine candidates.
Aim 2. Determine Group 2b vaccine candidate protection capacity against group 2b panel of viruses.
Aim 3. Develop PanbetaCoVMerbecovirus (group2c) vaccine candidates, determine their immunogenicity, cross- reactivity with other betaCoVs and protection capacity against group 2c panel of viruses. This program project grant includes four projects.
Project 1 will design vaccines in alphavirus replicon particle (VRP) vaccine system, develop and test P01 vaccines in their unique mouse CoV challenge models.
Project 2 will use structure-based molecular modeling and monomer and multimer nanoparticle spike protein designs and test in wild-type mouse models.
Project 3 will both design CoV vaccines and test vaccine designs expressed as mRNAs in liquid nanoparticles (LNPs).
Project 4 will computationally design B and T cell panbetaCoV vaccines. This P01 proposes three Cores: an Administrative Core, a Biocontainment and Immune Monitoring Core, and a Non-human Primate Core. Work in this P01 will provide panbetaCoV vaccines to protect against escape mutants of SARS-CoV-2 in the current epidemic, and will be available to protect society against new betaCoVs that might emerge to infect humans in the future.