PopCover-2.0. Improved Selection of Peptide Sets With Optimal HLA and Pathogen Diversity Coverage.
Front Immunol
; 12: 728936, 2021.
Article
in English
| MEDLINE | ID: covidwho-1413272
ABSTRACT
The use of minimal peptide sets offers an appealing alternative for design of vaccines and T cell diagnostics compared to conventional whole protein approaches. T cell immunogenicity towards peptides is contingent on binding to human leukocyte antigen (HLA) molecules of the given individual. HLA is highly polymorphic, and each variant typically presents a different repertoire of peptides. This polymorphism combined with pathogen diversity challenges the rational selection of peptide sets with broad immunogenic potential and population coverage. Here we propose PopCover-2.0, a simple yet highly effective method, for resolving this challenge. The method takes as input a set of (predicted) CD8 and/or CD4 T cell epitopes with associated HLA restriction and pathogen strain annotation together with information on HLA allele frequencies, and identifies peptide sets with optimal pathogen and HLA (class I and II) coverage. PopCover-2.0 was benchmarked on historic data in the context of HIV and SARS-CoV-2. Further, the immunogenicity of the selected SARS-CoV-2 peptides was confirmed by experimentally validating the peptide pools for T cell responses in a panel of SARS-CoV-2 infected individuals. In summary, PopCover-2.0 is an effective method for rational selection of peptide subsets with broad HLA and pathogen coverage. The tool is available at https//services.healthtech.dtu.dk/service.php?PopCover-2.0.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptides
/
Epitopes, T-Lymphocyte
/
HLA Antigens
Type of study:
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
Front Immunol
Year:
2021
Document Type:
Article
Affiliation country:
Fimmu.2021.728936
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