PT - JOURNAL ARTICLE AU - Malone, Brandon AU - Simovski, Boris AU - Moliné, Clément AU - Cheng, Jun AU - Gheorghe, Marius AU - Fontenelle, Hugues AU - Vardaxis, Ioannis AU - Tennøe, Simen AU - Malmberg, Jenny-Ann AU - Stratford, Richard AU - Clancy, Trevor TI - Artificial intelligence predicts the immunogenic landscape of SARS-CoV-2: toward universal blueprints for vaccine designs AID - 10.1101/2020.04.21.052084 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.04.21.052084 4099 - 4100 - AB - The global population is at present suffering from a pandemic of Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The goals of this study were to use artificial intelligence (AI) to predict blueprints for designing universal vaccines against SARS-CoV-2, that contain a sufficiently broad repertoire of T-cell epitopes capable of providing coverage and protection across the global population. To help achieve these aims, we profiled the entire SARS-CoV-2 proteome across the most frequent 100 HLA-A, HLA-B and HLA-DR alleles in the human population, using host-infected cell surface antigen presentation and immunogenicity predictors from the NEC Immune Profiler suite of tools, and generated comprehensive epitope maps. We then used these epitope maps as input for a Monte Carlo simulation designed to identify statistically significant “epitope hotspot” regions in the virus that are most likely to be immunogenic across a broad spectrum of HLA types. We then removed epitope hotspots that shared significant homology with proteins in the human proteome to reduce the chance of inducing off-target autoimmune responses. We also analyzed the antigen presentation and immunogenic landscape of all the nonsynonymous mutations across 3400 different sequences of the virus, to identify a trend whereby SARS-COV-2 mutations are predicted to have reduced potential to be presented by host-infected cells, and consequently detected by the host immune system. A sequence conservation analysis then removed epitope hotspots that occurred in less-conserved regions of the viral proteome. Finally, we used a database of the HLA genotypes of approximately 22 000 individuals to develop a “digital twin” type simulation to model how effective different combinations of hotspots would work in a diverse human population, and used the approach to identify an optimal constellation of epitopes hotspots that could provide maximum coverage in the global population. By combining the antigen presentation to the infected-host cell surface and immunogenicity predictions of the NEC Immune Profiler with a robust Monte Carlo and digital twin simulation, we have managed to profile the entire SARS-CoV-2 proteome and identify a subset of epitope hotspots that could be harnessed in a vaccine formulation to provide a broad coverage across the global population.Competing Interest StatementBS, CM, MG, HF, IV, ST, JM, RS and TC are employees of NEC OncoImmunity, a subsidiary of NEC Corporation. BM and JC are employees of NEC Laboratories Europe.