Sequence-based prediction of vaccine targets for inducing T cell responses to SARS-CoV-2 utilizing the bioinformatics predictor RECON

Asaf Poran; Dewi Harjanto; Matthew Malloy; Michael S. Rooney; Lakshmi Srinivasan; Richard B. Gaynor

1 high degree of sequence similarity allows us to leverage the previous research on protective 2 immune responses to SAR-CoV to aid in vaccine development for SARS-CoV-2. Both humoral 3 and cellular immune responses have been shown to be important in host responses to SARS-CoV 4 (12). Antibody responses generated against the S and the N proteins have shown to protect from 5 SARS-CoV infection in mice and have been detected in SARS-CoV infected patients (13-16). 6 However, these antibody responses detected against the S protein were short-lived and 7 undetectable in patients six years post-recovery, suggesting that T cell responses may be 8 involved in the long-term control of this virus (17). Indeed, significant changes in the total 9 lymphocyte counts and T cell subset composition have been observed in patients with SARS- 10 CoV; namely, levels of both B cells, and CD4 + and CD8 + T cells have been significantly reduced 11 in these patients (18, 19) . Similarly, mice infected with SARS-CoV demonstrated that the severity 12 of SARS correlated with the ability to develop a virus-specific T cell response (20, 21) . 13 Both CD4 + and CD8 + T cell responses have been detected in SARS-CoV-infected patients 14 (12,22) as well as in SARS-CoV-2 (23). Notably, SARS-CoV-specific memory CD8 + T cells 15 persisted up to 11 years post-infection in patients who recovered from SARS (24). Studies in 16 mice have shown that SARS-CoV-specific memory CD8 + T cells provided protection against a 17 lethal SARS-CoV infection in aged mice (21) . In addition, adoptive transfer of effector CD4 + 18 and CD8 + T cells to immunodeficient or young mice expedited virus clearance and improved 19 clinical results (20). Immunization with SARS-CoV peptide-pulsed dendritic cells invigorated a 20 T cell response, increasing the number of virus-specific CD8 + T cells enhancing both virus 21 clearance and overall survival (25). These studies indicate an important role for T cell responses 22 in controlling disease severity, virus clearance and conferring protective immunity to SARS-CoV 23 author/funder. All rights reserved. No reuse allowed without permission.