Induction of SARS-CoV-2 Protein S-Specific CD8+T Cells in the Lungs of gp96-Ig-S Vaccinated Mice

Given the aggressive spread of COVID-19-related deaths, there is an urgent public health need to support the development of vaccine candidates to rapidly improve the available control measures against SARS-CoV-2. To meet this need, we are leveraging our existing vaccine platform to target SARS-CoV-2. Here, we generated cellular heat shock chaperone protein, glycoprotein 96 (gp96), to deliver SARS-CoV-2 protein S (spike) to the immune system and to induce cell-mediated immune responses. We showed that our vaccine platform effectively stimulates a robust cellular immune response against protein S. Moreover, we confirmed that gp96-Ig, secreted from allogeneic cells expressing full-length protein S, generates powerful, protein S polyepitope-specific CD4+ and CD8+ T cell responses in both lung interstitium and airways. These findings were further strengthened by the observation that protein-S -specific CD8+ T cells were induced in human leukocyte antigen HLA-A2.1 transgenic mice thus providing encouraging translational data that the vaccine is likely to work in humans, in the context of SARS-CoV-2 antigen presentation.

Automated summary

This study leveraged cellular heat shock chaperone protein, gp96, to deliver SARS-CoV-2 protein S to the immune system, inducing cell-mediated immune responses. The vaccine platform effectively stimulated a robust cellular immune response against protein S, showing promising translational data for potential use in humans against SARS-CoV-2 antigen presentation.