PMID- 34484239 OWN - NLM STAT- MEDLINE DCOM- 20210915 LR - 20240403 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - PopCover-2.0. Improved Selection of Peptide Sets With Optimal HLA and Pathogen Diversity Coverage. PG - 728936 LID - 10.3389/fimmu.2021.728936 [doi] LID - 728936 AB - 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. CI - Copyright (c) 2021 Nilsson, Grifoni, Tarke, Sette and Nielsen. FAU - Nilsson, Jonas Birkelund AU - Nilsson JB AD - Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Lyngby, Denmark. FAU - Grifoni, Alba AU - Grifoni A AD - Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, United States. FAU - Tarke, Alison AU - Tarke A AD - Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, United States. AD - Department of Internal Medicine, University of Genoa, Genoa, Italy. AD - Department of Experimental Medicine, University of Genoa, Genoa, Italy. FAU - Sette, Alessandro AU - Sette A AD - Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, United States. FAU - Nielsen, Morten AU - Nielsen M AD - Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Lyngby, Denmark. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210817 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (Peptides) SB - IM MH - Alleles MH - Allergy and Immunology MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - COVID-19/immunology/prevention & control MH - Epitopes, T-Lymphocyte/*immunology MH - Genotype MH - HLA Antigens/classification/*genetics/*immunology MH - Humans MH - Immunogenicity, Vaccine MH - Immunologic Techniques MH - Peptides/classification/*immunology MH - SARS-CoV-2/immunology PMC - PMC8416060 OTO - NOTNLM OT - HLA OT - HLA class I OT - HLA class II OT - allelic coverage OT - epitope selection OT - pathogen coverage OT - rational epitope selection 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- 2021/09/07 06:00 MHDA- 2021/09/16 06:00 PMCR- 2021/08/17 CRDT- 2021/09/06 05:55 PHST- 2021/06/22 00:00 [received] PHST- 2021/07/30 00:00 [accepted] PHST- 2021/09/06 05:55 [entrez] PHST- 2021/09/07 06:00 [pubmed] PHST- 2021/09/16 06:00 [medline] PHST- 2021/08/17 00:00 [pmc-release] AID - 10.3389/fimmu.2021.728936 [doi] PST - epublish SO - Front Immunol. 2021 Aug 17;12:728936. doi: 10.3389/fimmu.2021.728936. eCollection 2021.