Induction of SARS-CoV-2 protein S-specific CD8+ T cells in the lungs of gp96-Ig-S vaccinated mice

Abstract

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)-A2-02-01 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.

Recombinant protein vaccines, a proven approach against coronavirus pandemics

“…In mice, the vaccine induced tissue-resident memory T (TRM) cells, capable of rapidly responding to infection in the tissue. It also elicited CD4+ and CD8+T cell responses that are specific to the S-protein epitopes in the lung interstitium and the airways [ 166 ]. Unlike other COVID-19 vaccines, this vaccine technology provided an approach to induce the desired cellular response directly in the target tissues.…”

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

“…This manuscript has been released as a pre-print at bioRxiv ( 65 ). We dedicate this work to the late Dr. Eckhard Podack.…”