PopCover-2.0. Improved Selection of Peptide Sets With Optimal HLA and Pathogen Diversity Coverage

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Sep 6

PMID 34484239

Citations 4

Authors

Jonas Birkelund Nilsson

Alba Grifoni

Alison Tarke

Alessandro Sette

Morten Nielsen

Affiliations

Soon will be listed here.

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.

Citing Articles

In Silico Tools for Predicting Novel Epitopes.

Barra C, Nilsson J, Saksager A, Carri I, Deleuran S, Garcia Alvarez H Methods Mol Biol. 2024; 2813:245-280.

PMID: 38888783 DOI: 10.1007/978-1-0716-3890-3_17.

Prevalent and immunodominant CD8 T cell epitopes are conserved in SARS-CoV-2 variants.

Meyer S, Blaas I, Bollineni R, Delic-Sarac M, Tran T, Knetter C Cell Rep. 2023; 42(1):111995.

PMID: 36656713 PMC: 9826989. DOI: 10.1016/j.celrep.2023.111995.

Immunoinformatics Analysis of Citrullinated Antigen as Potential Multi-peptide Lung Cancer Vaccine Candidates for Indonesian Population.

Hermawan A, Damai F, Martin L, Chrisdianto M, Julianto N, Pramanda I Int J Pept Res Ther. 2022; 28(6):162.

PMID: 36406283 PMC: 9648882. DOI: 10.1007/s10989-022-10467-1.

Peptide-Based Vaccines for Tuberculosis.

Gong W, Pan C, Cheng P, Wang J, Zhao G, Wu X Front Immunol. 2022; 13:830497.

PMID: 35173740 PMC: 8841753. DOI: 10.3389/fimmu.2022.830497.

References

Theiler J, Yoon H, Yusim K, Picker L, Fruh K, Korber B . Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. Sci Rep. 2016; 6:33987. PMC: 5050445. DOI: 10.1038/srep33987. View

Toussaint N, Kohlbacher O . OptiTope--a web server for the selection of an optimal set of peptides for epitope-based vaccines. Nucleic Acids Res. 2009; 37(Web Server issue):W617-22. PMC: 2703925. DOI: 10.1093/nar/gkp293. View

Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin J, Olsson A . Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020; 183(1):158-168.e14. PMC: 7427556. DOI: 10.1016/j.cell.2020.08.017. View

Grifoni A, Weiskopf D, Ramirez S, Mateus J, Dan J, Rydyznski Moderbacher C . Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020; 181(7):1489-1501.e15. PMC: 7237901. DOI: 10.1016/j.cell.2020.05.015. View

Ott P, Hu Z, Keskin D, Shukla S, Sun J, Bozym D . An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017; 547(7662):217-221. PMC: 5577644. DOI: 10.1038/nature22991. View

Peters B, Nielsen M, Sette A . T Cell Epitope Predictions. Annu Rev Immunol. 2020; 38:123-145. PMC: 10878398. DOI: 10.1146/annurev-immunol-082119-124838. View

Jiang M, Guo Y, Luo Q, Huang Z, Zhao R, Liu S . T-Cell Subset Counts in Peripheral Blood Can Be Used as Discriminatory Biomarkers for Diagnosis and Severity Prediction of Coronavirus Disease 2019. J Infect Dis. 2020; 222(2):198-202. PMC: 7239156. DOI: 10.1093/infdis/jiaa252. View

Nielsen M, Andreatta M, Peters B, Buus S . Immunoinformatics: Predicting Peptide-MHC Binding. Annu Rev Biomed Data Sci. 2023; 3:191-215. PMC: 10328453. DOI: 10.1146/annurev-biodatasci-021920-100259. View

Yossef R, Tran E, Deniger D, Gros A, Pasetto A, Parkhurst M . Enhanced detection of neoantigen-reactive T cells targeting unique and shared oncogenes for personalized cancer immunotherapy. JCI Insight. 2018; 3(19). PMC: 6237474. DOI: 10.1172/jci.insight.122467. View

10.

Petrone L, Petruccioli E, Vanini V, Cuzzi G, Fard S, Alonzi T . A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients. Clin Microbiol Infect. 2020; 27(2):286.e7-286.e13. PMC: 7547312. DOI: 10.1016/j.cmi.2020.09.051. View

11.

Schubert B, Lund O, Nielsen M . Evaluation of peptide selection approaches for epitope-based vaccine design. Tissue Antigens. 2014; 82(4):243-51. DOI: 10.1111/tan.12199. View

12.

Vider-Shalit T, Raffaeli S, Louzoun Y . Virus-epitope vaccine design: informatic matching the HLA-I polymorphism to the virus genome. Mol Immunol. 2006; 44(6):1253-61. DOI: 10.1016/j.molimm.2006.06.003. View

13.

Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R . Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med. 2006; 13(1):100-6. DOI: 10.1038/nm1461. View

14.

Gonzalez-Galarza F, McCabe A, Melo Dos Santos E, Jones J, Takeshita L, Ortega-Rivera N . Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools. Nucleic Acids Res. 2019; 48(D1):D783-D788. PMC: 7145554. DOI: 10.1093/nar/gkz1029. View

15.

Ondondo B, Murakoshi H, Clutton G, Abdul-Jawad S, Wee E, Gatanaga H . Novel Conserved-region T-cell Mosaic Vaccine With High Global HIV-1 Coverage Is Recognized by Protective Responses in Untreated Infection. Mol Ther. 2016; 24(4):832-42. PMC: 4886941. DOI: 10.1038/mt.2016.3. View

16.

Saini S, Hersby D, Tamhane T, Povlsen H, Amaya Hernandez S, Nielsen M . SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 T cell activation in COVID-19 patients. Sci Immunol. 2021; 6(58). PMC: 8139428. DOI: 10.1126/sciimmunol.abf7550. View

17.

Toussaint N, Maman Y, Kohlbacher O, Louzoun Y . Universal peptide vaccines - optimal peptide vaccine design based on viral sequence conservation. Vaccine. 2011; 29(47):8745-53. DOI: 10.1016/j.vaccine.2011.07.132. View

18.

Keskin D, Anandappa A, Sun J, Tirosh I, Mathewson N, Li S . Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2018; 565(7738):234-239. PMC: 6546179. DOI: 10.1038/s41586-018-0792-9. View

19.

Robinson J, Barker D, Georgiou X, Cooper M, Flicek P, Marsh S . IPD-IMGT/HLA Database. Nucleic Acids Res. 2019; 48(D1):D948-D955. PMC: 7145640. DOI: 10.1093/nar/gkz950. View

20.

Gonzalez-Galarza F, McCabe A, Melo Dos Santos E, Takeshita L, Ghattaoraya G, Jones A . Allele Frequency Net Database. Methods Mol Biol. 2018; 1802:49-62. DOI: 10.1007/978-1-4939-8546-3_4. View