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.

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Copyright © 2021 Fisher, Padula, Podack, O’Neill, Seavey, Jayaraman, Jasuja and Strbo.

Déclaration de conflit d'intérêts

NS is inventor on the patent application No 62/983,783 entitled “Immune-mediated coronavirus treatments”; NS is a member of Heat Biologics COVID-19 Advisory Board. MS is the Executive Director of Special Projects. PJ is the Associate Director of Business Development, both are employed by Heat Biologics, Inc. RJ is the CEO of Pelican Therapeutics, a subsidiary of Heat Biologics, Inc. MS, PJ, RJ, and KP hold stock options in Heat Biologics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.