SARS-CoV-2 Consensus-Sequence and Matching Overlapping Peptides Design for COVID19 Immune Studies and Vaccine Development

Abstract

Synthetic antigens based on consensus sequences that represent circulating viral isolates are sensitive, time saving and cost-effective tools for in vitro immune monitoring and to guide immunogen design. When based on a representative sequence database, such consensus sequences can effectively be used to test immune responses in exposed and infected individuals at the population level. To accelerate immune studies in SARS-CoV-2 infection, we here describe a SARS-CoV-2 2020 consensus sequence (CoV-2-cons) which is based on more than 1700 viral genome entries in NCBI and encompasses all described SARS-CoV-2 open reading frames (ORF), including recently described frame-shifted and length variant ORF. Based on these sequences, we created curated overlapping peptide (OLP) lists containing between 1500 to 3000 peptides of 15 and 18 amino acids in length, overlapping by 10 or 11 residues, as ideal tools for the assessment of SARS-CoV-2-specific T cell immunity. In addition, CoV-2-cons sequence entropy values are presented along with variant sequences to provide increased coverage of the most variable sections of the viral genome. The identification of conserved protein fragments across the coronavirus family and the corresponding OLP facilitate the identification of T cells potentially cross-reactive with related viruses. This new CoV-2-cons sequence, together with the peptides sets, should provide the basis for SARS-CoV-2 antigen synthesis to facilitate comparability between ex-vivo immune analyses and help to accelerate research on SARS-CoV-2 immunity and vaccine development.

Mass spectrometric identification of immunogenic SARS-CoV-2 epitopes and cognate TCRs

“…Newly Defined Epitopes Are Found in Highly Conserved Regions of SARS-CoV-2 and SARS-CoV-2 Variants. Olvera et al (24) recently described the development of a COVID-19 vaccine using the overlapping of SARS-CoV-2 consensus sequences. Olvera et al utilized an entropy-based calculation on more than 1,700 viral genome entries in the National Center for Biotechnology Information database and encompassed all described SARS-CoV-2 open reading frames (ORFs), including recently described frame-shifted and length-variant ORFs.…”

One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages

“…Interestingly, and potentially benefiting protection through cross reaction, some epitopes from S and N proteins map identically in SARS-CoV-1 and SARS-CoV-2 ( Ahmed et al, 2020 ). Identification of SARS-CoV-2 specific T cell epitopes, including those encompassing the new variants, as well as epitopes recognised by T cells potentially cross reactive with related viruses will be key for understanding immunity and immunopathological sequelae, which will impact on vaccine design ( Flanagan et al, 2020 ; Ahmed et al, 2020 ; Olvera et al, 2020 ).…”

Immunogenic SARS-CoV2 Epitopes Defined by Mass Spectrometry

“…Olvera et. al recently described the development of a COVID19 vaccine using the overlapping of SARS-CoV-2 consensus sequence (24). This paper utilized an entropy-based calculation on more than 1700 viral genome entries in NCBI and encompassed all described SARS-CoV-2 open reading frames (ORF), including recently described frame-shifted and length variant ORF.…”