key: cord-0758745-90f8spxe authors: Ahmed, Syed Faraz; Quadeer, Ahmed A.; McKay, Matthew R. title: COVIDep: A web-based platform for real-time reporting of vaccine target recommendations for SARS-CoV-2 date: 2020-05-24 journal: bioRxiv DOI: 10.1101/2020.05.23.111385 sha: d8e4962035ab87b01f850f54a836fa5cbb4e5f23 doc_id: 758745 cord_uid: 90f8spxe We introduce COVIDep (https://COVIDep.ust.hk), a web-based platform that provides immune target recommendations for guiding SARS-CoV-2 vaccine development. COVIDep implements a protocol that pools together publicly-available genetic data for SARS-CoV-2 and epitope data for SARS-CoV to identify B cell and T cell epitopes that present potential immune targets for SARS-CoV-2. Correspondences between outputs of COVIDep and emerging experimental results are also indicated. The platform is user-friendly, flexible, and based on up-to-date data. It may help guide vaccine designs and associated experimental studies for SARS-CoV-2. The vaccine targets recommended by COVIDep exploit the genetic similarities between SARS-CoV-2 and SARS-CoV, along with known immune targets for SARS-CoV that have been determined experimentally. The system implements a protocol that identifies from among the SARS epitopes that can induce a human immune response, those that are genetically similar in SARS-CoV-2. This idea, put forward in our preliminary study 1 based on limited early data, identified known SARS-CoV epitopes that had an identical genetic match in SARS-CoV-2. These epitopes presented initial vaccine target recommendations for potentially eliciting a protective, cross-reactive immune response against SARS-CoV-2. Similar ideas and results were reported subsequently in an independent study 2 . The use of SARS-CoV immunological data to inform vaccine targets for SARS-CoV-2 is being supported by experimental results. There is evidence of SARS-CoV-derived antibodies binding to genetically similar regions of SARS-CoV-2's spike protein 3 , and also of cross-neutralization [4] [5] [6] . Conversely, studies have demonstrated that specific SARS-CoV-derived antibodies binding to the spike's receptor binding domain, which has significant genetic differences in SARS-CoV-2, have limited cross-reactivity 7 . Antibody and T cell responses against spike protein epitopes that are genetically similar in SARS-CoV and SARS-CoV-2 have also been reported in COVID-19 infected patients 8, 9 , and in preclinical vaccine trials 10,11 . Epitopes recommended by COVIDep have notable overlap with the findings in these experimental studies (Figures 2 and 3 ). The recommendations provided by COVIDep may be used to guide vaccine designs and associated experimental studies, and may help to expedite the discovery of an effective vaccine for COVID-19. The SARS-CoV-2 full genome sequence data is periodically downloaded from the Global Initiative on Sharing Avian Influenza Database (GISAID; www.gisaid.org). The SARS-CoV epitope sequence data was downloaded from the Virus Pathogen Database and Analysis Resource (ViPR; www.viprbrc.org). The population coverage statistics of HLA alleles were obtained from the Immune Epitope Database and Analysis Resource (IEDB; www.iedb.org). The source code for the developed platform is available at the COVIDep GitHub repository (https://github.com/COVIDep). and their overlap with emerging experimental results. The majority of the identified epitopes (24/29; shown in a shaded box) are located in the S2 functional subunit of the spike protein, reported to be a main region targeted by crossreactive 3 and cross-neutralizing 4 antibodies. The epitopes with IEDB IDs 70719 and 15972 overlap with regions in the S1 functional subunit of the spike protein reported to be targeted by cross-neutralizing antibodies 5,6 . The specific overlapping residues are underlined. The epitopes with IEDB IDs 9094, 12426, and 558417 overlap with an epitope (located at positions 1178-1189) reported to be targeted by neutralizing antibodies in a preclinical trial of a SARS-CoV-2 vaccine candidate 10 . Interestingly, the partial overlaps of the (consecutive) epitopes 9094 and 12426/558417 cover the experimentally-reported epitope 10 completely. Note that epitopes 12426 and 558417 share the same sequence; they have different IDs in the IEDB database due to differences in the associated experimental procedures. The epitopes with IEDB IDs 52020 and 16183 overlap with the regions reported to be recognized by neutralizing antibodies in the sera of recovered COVID-19 patients 8 . 9 . The specific overlapping residues are underlined. In a preclinical vaccine trial 11 , T cell responses have also been recorded against a protein region comprising the identified epitope with IEDB ID 71663. The epitopes with IEDB IDs 36724 and 71663 were originally reported based on positive T cell assays for SARS-CoV, while those with IEDB IDs 54507, 54725, and 37289 were reported based on positive MHC binding assays. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2 Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newlyemerged SARS-CoV-2 Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein A human monoclonal antibody blocking SARS-CoV-2 infection Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein Shared antigen-specific CD8+ T cell responses against the SARS-COV-2 spike protein in HLA A*02:01 COVID-19 participants Immunogenicity of a DNA vaccine candidate for COVID-19 COVIDep is made possible by the open sharing of genome sequence data of SARS-CoV-2 sequences by research groups from around the world through the GISAID platform, and the open sharing of immunological data of experimentally-determined SARS-CoV epitopes through the ViPR database. We gratefully acknowledge the contributions of all the researchers, scientists and technical staff involved (a detailed acknowledgment is available at the Acknowledgments page of the COVIDep platform).We thank Nelvin Law and Kenny Pang for their technical support, and Raymond Louie, David Morales-Jimenez, Saqib Sohail, Neelkanth Kundu, Awais Shah, and Umer Abdullah for comments and suggestions that helped to improve the web application and its interface. COVIDep periodically pools SARS-CoV-2 sequence data and compares with experimentally-determined B cell and T cell epitopes of SARS-CoV. The system outputs those epitopes that are genetically similar in SARS-CoV-2, based on an epitope screening parameter. This user-defined parameter allows the user to select epitopes based on their conservation in the SARS-CoV-2 sequence data, where conservation is defined as the fraction of SARS-CoV-2 sequences with the exact epitope sequence. For the identified T cell epitopes, population coverage analysis is performed to estimate the percentage of a specified population that can elicit a response against them.