Mining of linear B cell epitopes of SARS-CoV-2 ORF8 protein from COVID-19 patients

Abstract

The landscape of linear B cell epitopes of SARS-CoV-2 ORF8 protein is determined by analysing serum IgG response of COVID-19 patients ABSTRACT Given the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the viral protein will provide crucial advances towards the development of sensitive diagnostic tools and vaccination strategies. Our previous study has found that ORF8 protein of SARS-CoV-2 is highly immunogenic and shows high sensitivity in identifying COVID-19 disease.In this study, by employing overlapping linear peptides, we characterized the IgG immunodominant regions on SARS-CoV-2 ORF8 protein that are seropositive in the sera from SARS-CoV-2-infected patients. The major immunogenic epitopes are localised at 1) Ntermini alpha helix, 2) the resides spanning beta 2 and 3 sheets, and 3) the loop between beta 4 and 5 sheets. Additionally, hamster model infected by SARS-CoV-2 further validate the seropositivity of the linear epitopes in-vivo, demonstrating a potential application of the linear peptide-based immunization strategy. Taken together, identification and validation of these Bcell linear epitopes will provide insights towards the design of serological diagnostics and peptide-based vaccination approach against this pandemic virus of high priority.

ELISA-Based Analysis Reveals an Anti-SARS-CoV-2 Protein Immune Response Profile Associated with Disease Severity

“…Many studies have been performed to identify B-cell linear epitopes in the SARS-CoV-2 proteins [18,19,[26][27][28][29][30][31][32][33][34][35][36][37]. Our study confirms previous findings, identifying the same overall regions.…”

“…These epitopes are important for diagnosis, for the development of monoclonal antibodies for prevention and treatment, and for the design of peptide-based vaccines [14][15][16]. Several immunodominant linear epitopes have been identified on the S, M, E, N (for review [17]) and ORF8 [18] proteins. However, only a few studies have investigated the possible correlation between specific reactivity to particular linear epitopes and disease severity [19][20][21].…”

Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8

“…Previous studies have shown that antibodies and peptides against ORF8 are readily detected in the sera of COVID-19 patients ( 25 , 26 ), suggesting that ORF8 is a secreted viral protein with highly immunogenic properties ( 29 ). We found that ORF8 was readily detected in lung bronchial epithelial cells of SARS-CoV-2-infected ferrets and mice ( Fig.…”

“…The SARS-CoV-2 ORF8 consists of 121 amino acids, including an N-terminal signal peptide (1 to 15 aa) and a C-terminal immunoglobulin (Ig)-like domain (16 to 121 aa). It has been identified as a secreted, highly immunogenic, and rapidly evolving protein ( 24 – 26 ). Sequence alignment shows that the SARS-CoV-2 ORF8 shares high similarity with Bat-RaTG13-CoV ORF8 (95%) but low similarity with SARS-CoV ORF8 (30%), suggesting that SARS-CoV-2 ORF8 may have originated from the Bat-RaTG13-CoV ORF8 ( 27 ).…”

Designing a New Multiepitope-based Vaccine Against COVID-19

“…Recently, most developed or under developing vaccines have focused on virus surface proteins such as spike and nucleocapsid protein. These proteins show good immunity, but some studies have indicated the high immunogenicity of the ORF8 protein [19]. Also, the ORF7b and ORF10 proteins are unique, and they lacked any sequence homology with other viral proteins [20].…”