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.
Highlights
Since the start of the COVID-19 pandemic in December 2019, researchers around the world have put major efforts towards a better understanding of the immune response to its causative agent, the SARS-CoV-2
Of the 23 open reading frames (ORF), 12 were canonical ORF as annotated in NC_045512.2 and 11 in alternative reading frames described by Finkel et al [46] (Table 1)
In addition to variable positions, we evaluated the presence of protein regions conserved among coronavirus species, as these may support the design of immunogen sequences for pan-coronavirus vaccines
Summary
Since the start of the COVID-19 pandemic in December 2019, researchers around the world have put major efforts towards a better understanding of the immune response to its causative agent, the SARS-CoV-2. An impressive amount of scientific information has been generated in a very short period of time, there remain significant gaps in our understanding of SARS-CoV-2 immune control. It remains unclear what kind of adaptive immunity should be triggered by vaccination in order to achieve sterile immunity, or at least lead to an ameliorated disease course, in cases where. We know from the available literature on other coronaviruses (mainly SARS-CoV-1 and MERS) that antibodies can neutralize the infection, these humoral responses are short lived in many individuals, and that long-lived T cells responses are present in people with less severe disease outcomes [1,2,3,4,5]. Improved tools to assess host T cell immunity in detail are urgently needed to better identify these responses and to define their role in the outcome of SARS-CoV-2 infection
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