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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.
Oyarzun, Patricio; Kashyap, Manju; Fica, Victor; Salas-Burgos, Alexis; Gonzalez-Galarza, Faviel F; McCabe, Antony; Jones, Andrew R; Middleton, Derek; Kobe, Bostjan.
  • Oyarzun P; Facultad de Ingeniería y Tecnología, Universidad San Sebastián, Sede Concepción, Concepción, Chile.
  • Kashyap M; Facultad de Ingeniería y Tecnología, Universidad San Sebastián, Sede Concepción, Concepción, Chile.
  • Fica V; Facultad de Ingeniería y Tecnología, Universidad San Sebastián, Sede Concepción, Concepción, Chile.
  • Salas-Burgos A; Departmento of Farmacología, Universidad de Concepción, Concepción, Chile.
  • Gonzalez-Galarza FF; Center for Biomedical Research, Faculty of Medicine, Autonomous University of Coahuila, Torreon, Mexico.
  • McCabe A; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
  • Jones AR; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
  • Middleton D; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
  • Kobe B; School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia.
Front Immunol ; 12: 598778, 2021.
Article in English | MEDLINE | ID: covidwho-1133909
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: CD4-Positive T-Lymphocytes / Ethnicity / CD8-Positive T-Lymphocytes / Epitopes, T-Lymphocyte / Proteomics / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / HLA Antigens Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Humans Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.598778

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Full text: Available Collection: International databases Database: MEDLINE Main subject: CD4-Positive T-Lymphocytes / Ethnicity / CD8-Positive T-Lymphocytes / Epitopes, T-Lymphocyte / Proteomics / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / HLA Antigens Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Humans Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.598778