{"doi":"10.1101/2020.09.27.316018","title":"Genome-Wide Asymptomatic B-Cell, CD4 <sup>+</sup> and CD8 <sup>+</sup> T-Cell Epitopes, that are Highly Conserved Between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Immune Targets for Pre-Emptive Pan-Coronavirus Vaccines","abstract":"ABSTRACT Over the last two decades, there have been three deadly human outbreaks of Coronaviruses (CoVs) caused by emerging zoonotic CoVs: SARS-CoV, MERS-CoV, and the latest highly transmissible and deadly SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats, the natural hosts, and transmitted to humans via various intermediate animal reservoirs. Because there is currently no universal pan-Coronavirus vaccine available, two worst-case scenarios remain highly possible: (1) SARS-CoV-2 mutates and transforms into a seasonal “flu-like” global pandemic; and/or (2) Other global COVID-like pandemics will emerge in the coming years, caused by yet another spillover of an unknown zoonotic bat-derived SARS-like Coronavirus (SL-CoV) into an unvaccinated human population. Determining the antigen and epitope landscapes that are conserved among human and animal Coronaviruses as well as the repertoire, phenotype and function of B cells and CD4 + and CD8 + T cells that correlate with resistance seen in asymptomatic COVID-19 patients should inform in the development of pan-Coronavirus vaccines 1 . In the present study, using several immuno-informatics and sequence alignment approaches, we identified several human B-cell, CD4 + and CD8 + T cell epitopes that are highly conserved in: ( i ) greater than 81,000 SARS-CoV-2 human strains identified to date in 190 countries on six continents; ( ii ) six circulating CoVs that caused previous human outbreaks of the “Common Cold”; ( iii ) five SL-CoVs isolated from bats; ( iv ) five SL-CoV isolated from pangolins; ( v ) three SL-CoVs isolated from Civet Cats; and ( vi ) four MERS strains isolated from camels. Furthermore, we identified cross-reactive asymptomatic epitopes that: ( i ) recalled B cell, CD4 + and CD8 + T cell responses from both asymptomatic COVID-19 patients and healthy individuals who were never exposed to SARS-CoV-2; and ( ii ) induced strong B cell and T cell responses in “humanized” Human Leukocyte Antigen (HLA)-DR/HLA-A*02:01 double transgenic mice. The findings herein pave the way to develop a pre-emptive multi-epitope pan-Coronavirus vaccine to protect against past, current, and potential future outbreaks.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124066,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":528443,"name":"Ruchi Srivastava","orcid":"0000-0003-3112-4252","position":1,"is_corresponding":false},{"id":528444,"name":"Pierre‐Grégoire Coulon","orcid":"0000-0001-6458-8710","position":2,"is_corresponding":false},{"id":528445,"name":"Nisha R. Dhanushkodi","orcid":"0000-0001-8184-4050","position":3,"is_corresponding":false},{"id":568276,"name":"Aziz Alami Chentoufi","orcid":"0000-0002-5410-2593","position":4,"is_corresponding":false},{"id":522461,"name":"Delia F. Tifrea","orcid":"0000-0002-7531-9337","position":5,"is_corresponding":false},{"id":347748,"name":"Robert A. Edwards","orcid":"0000-0001-9145-382X","position":6,"is_corresponding":false},{"id":565920,"name":"Cesar Figueroa","orcid":"0000-0001-5538-5698","position":7,"is_corresponding":false},{"id":565919,"name":"Sebastian D. Schubl","orcid":"0000-0001-9431-7735","position":8,"is_corresponding":false},{"id":103439,"name":"Lanny Hsieh","orcid":null,"position":9,"is_corresponding":false},{"id":235603,"name":"Michael J. Buchmeier","orcid":"0000-0002-2387-9287","position":10,"is_corresponding":false},{"id":568277,"name":"Mohammed Bouziane","orcid":"0000-0003-2578-1280","position":11,"is_corresponding":false},{"id":569223,"name":"Anthony B. Nesburn","orcid":null,"position":12,"is_corresponding":false},{"id":569224,"name":"Baruch D. Kuppermann","orcid":null,"position":13,"is_corresponding":false},{"id":528448,"name":"Lbachir BenMohamed","orcid":"0000-0001-9468-2521","position":14,"is_corresponding":false},{"id":61323,"name":"Swayam Prakash","orcid":"0000-0003-3986-890X","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-18T23:15:07.789881Z","pmid":"33024971","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}