Immunoinformatic Analysis of SARS-CoV-2 Nucleocapsid Protein and Identification of COVID-19 Vaccine Targets.

Sergio C Oliveira,Mariana T Q De Magalhães,E Jane Homan

doi:10.3389/fimmu.2020.587615

Sergio C Oliveira, Mariana T Q De Magalhães + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2020.587615

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Abstract

COVID-19 is a worldwide emergency; therefore, there is a critical need for foundational knowledge about B and T cell responses to SARS-CoV-2 essential for vaccine development. However, little information is available defining which determinants of SARS-CoV-2 other than the spike glycoprotein are recognized by the host immune system. In this study, we focus on the SARS-CoV-2 nucleocapsid protein as a suitable candidate target for vaccine formulations. Major B and T cell epitopes of the SARS-CoV-2 N protein are predicted and resulting sequences compared with the homolog immunological domains of other coronaviruses that infect human beings. The most dominant of B cell epitope is located between 176–206 amino acids in the SRGGSQASSRSSSRSRNSSRNSTPGSSRGTS sequence. Further, we identify sequences which are predicted to bind multiple common MHC I and MHC II alleles. Most notably there is a region of potential T cell cross-reactivity within the SARS-CoV-2 N protein position 102–110 amino acids that traverses multiple human alpha and betacoronaviruses. Vaccination strategies designed to target these conserved epitope regions could generate immune responses that are cross-reactive across human coronaviruses, with potential to protect or modulate disease. Finally, these predictions can facilitate effective vaccine design against this high priority virus.

Highlights

The pandemic Coronavirus Disease 2019 (COVID-19) is a worldwide threat caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]
We focus on the SARS-CoV-2 nucleocapsid protein that is involved in viral pathogenesis [4, 17]
The nucleocapsid of SARS-Cov-2 exhibits both strong B and T cell epitopes distributed across the whole protein

Summary

Introduction

The pandemic Coronavirus Disease 2019 (COVID-19) is a worldwide threat caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. The RBD binds to ACE2 as its host cell target receptor, which allows virus entry [5, 7]. Various reports related to SARS-CoV2 suggest a correlation between neutralizing antibodies and the number of specific T cells to viral particles [8]. Most vaccine studies so far have focused on antibody responses generated against the S protein, the most exposed protein of SARS-CoV-2 [10, 11]. Previous studies with SARS-CoV-1 have shown that memory B cell responses tend to be short-lived after infection [13]. Memory T cell responses can persist for many years [14], and in mice, these protect against lethal challenge with SARS-CoV-1 [13]. The spike protein has several hotspots for mutations [15], whereas the nucleocapsid gene is more stable and has acquired fewer mutations to date [16]

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