PMID- 33717077 OWN - NLM STAT- MEDLINE DCOM- 20210318 LR - 20211204 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - A Proteome-Wide Immunoinformatics Tool to Accelerate T-Cell Epitope Discovery and Vaccine Design in the Context of Emerging Infectious Diseases: An Ethnicity-Oriented Approach. PG - 598778 LID - 10.3389/fimmu.2021.598778 [doi] LID - 598778 AB - Emerging infectious diseases (EIDs) caused by viruses are increasing in frequency, causing a high disease burden and mortality world-wide. The COVID-19 pandemic caused by the novel SARS-like coronavirus (SARS-CoV-2) underscores the need to innovate and accelerate the development of effective vaccination strategies against EIDs. Human leukocyte antigen (HLA) molecules play a central role in the immune system by determining the peptide repertoire displayed to the T-cell compartment. Genetic polymorphisms of the HLA system thus confer a strong variability in vaccine-induced immune responses and may complicate the selection of vaccine candidates, because the distribution and frequencies of HLA alleles are highly variable among different ethnic groups. Herein, we build on the emerging paradigm of rational epitope-based vaccine design, by describing an immunoinformatics tool (Predivac-3.0) for proteome-wide T-cell epitope discovery that accounts for ethnic-level variations in immune responsiveness. Predivac-3.0 implements both CD8+ and CD4+ T-cell epitope predictions based on HLA allele frequencies retrieved from the Allele Frequency Net Database. The tool was thoroughly assessed, proving comparable performances (AUC ~0.9) against four state-of-the-art pan-specific immunoinformatics methods capable of population-level analysis (NetMHCPan-4.0, Pickpocket, PSSMHCPan and SMM), as well as a strong accuracy on proteome-wide T-cell epitope predictions for HIV-specific immune responses in the Japanese population. The utility of the method was investigated for the COVID-19 pandemic, by performing in silico T-cell epitope mapping of the SARS-CoV-2 spike glycoprotein according to the ethnic context of the countries where the ChAdOx1 vaccine is currently initiating phase III clinical trials. Potentially immunodominant CD8+ and CD4+ T-cell epitopes and population coverages were predicted for each population (the Epitope Discovery mode), along with optimized sets of broadly recognized (promiscuous) T-cell epitopes maximizing coverage in the target populations (the Epitope Optimization mode). Population-specific epitope-rich regions (T-cell epitope clusters) were further predicted in protein antigens based on combined criteria of epitope density and population coverage. Overall, we conclude that Predivac-3.0 holds potential to contribute in the understanding of ethnic-level variations of vaccine-induced immune responsiveness and to guide the development of epitope-based next-generation vaccines against emerging pathogens, whose geographic distributions and populations in need of vaccinations are often well-defined for regional epidemics. CI - Copyright (c) 2021 Oyarzun, Kashyap, Fica, Salas-Burgos, Gonzalez-Galarza, McCabe, Jones, Middleton and Kobe. FAU - Oyarzun, Patricio AU - Oyarzun P AD - Facultad de Ingenieria y Tecnologia, Universidad San Sebastian, Sede Concepcion, Concepcion, Chile. FAU - Kashyap, Manju AU - Kashyap M AD - Facultad de Ingenieria y Tecnologia, Universidad San Sebastian, Sede Concepcion, Concepcion, Chile. FAU - Fica, Victor AU - Fica V AD - Facultad de Ingenieria y Tecnologia, Universidad San Sebastian, Sede Concepcion, Concepcion, Chile. FAU - Salas-Burgos, Alexis AU - Salas-Burgos A AD - Departmento of Farmacologia, Universidad de Concepcion, Concepcion, Chile. FAU - Gonzalez-Galarza, Faviel F AU - Gonzalez-Galarza FF AD - Center for Biomedical Research, Faculty of Medicine, Autonomous University of Coahuila, Torreon, Mexico. FAU - McCabe, Antony AU - McCabe A AD - Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom. FAU - Jones, Andrew R AU - Jones AR AD - Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom. FAU - Middleton, Derek AU - Middleton D AD - Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom. FAU - Kobe, Bostjan AU - Kobe B AD - School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210226 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (COVID-19 Vaccines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (Spike Glycoprotein, Coronavirus) SB - IM MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - COVID-19/epidemiology/*immunology MH - COVID-19 Vaccines MH - Communicable Diseases, Emerging MH - Epitopes, T-Lymphocyte/genetics/*metabolism MH - *Ethnicity MH - HLA Antigens/genetics/*metabolism MH - Humans MH - Immunogenicity, Vaccine MH - Medical Informatics Applications MH - Pandemics/prevention & control MH - Polymorphism, Genetic MH - Protein Binding MH - Proteomics/*methods MH - SARS-CoV-2/*physiology MH - Software MH - Spike Glycoprotein, Coronavirus/genetics/*metabolism PMC - PMC7952308 OTO - NOTNLM OT - SARS-CoV-2 OT - T-cell epitope OT - emerging-infectious disease OT - epitope discovery OT - ethnicity OT - immunoinformatics OT - vaccine design COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/03/16 06:00 MHDA- 2021/03/19 06:00 PMCR- 2021/02/26 CRDT- 2021/03/15 06:57 PHST- 2020/08/25 00:00 [received] PHST- 2021/01/11 00:00 [accepted] PHST- 2021/03/15 06:57 [entrez] PHST- 2021/03/16 06:00 [pubmed] PHST- 2021/03/19 06:00 [medline] PHST- 2021/02/26 00:00 [pmc-release] AID - 10.3389/fimmu.2021.598778 [doi] PST - epublish SO - Front Immunol. 2021 Feb 26;12:598778. doi: 10.3389/fimmu.2021.598778. eCollection 2021.