Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2019 Nov 28

PMID 31775024

Citations 7

Authors

Jonathan Powlson

Daniel Wright

Antra Zeltina

Mark Giza

Morten Nielsen

Tommy Rampling

Navin Venkatrakaman

Thomas A Bowden

Adrian V S Hill

Katie J Ewer

Affiliations

Soon will be listed here.

Abstract

Ebolavirus causes highly lethal hemorrhagic fever in humans. The envelope-displayed viral glycoprotein (GP) is the primary target of humoral immunity induced by natural exposure and vaccination. No T cell epitopes in the GP have been characterized in humans. A phase I clinical trial of a heterologous prime-boost vaccination regime with viral vectors encoding filovirus antigens elicits humoral and T cell responses in vaccinees. The most frequently recognized peptide pools are deconvoluted to identify the minimal epitopes recognized by antigen-specific T cells. We characterize nine immunogenic epitopes on the Ebolavirus GP. Histocompatibility leukocyte antigen (HLA) typing with in silico epitope analysis determines the likely MHC class I restriction elements. Thirteen HLA-A and -B alleles are predicted to present the identified CD8 T cell epitopes, suggesting promiscuous recognition and a broad immune response. Delivery of the Ebolavirus GP antigen by using a heterologous prime-boost approach is immunogenic in genetically diverse human populations, with responses against multiple epitopes.

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References

Pettitt J, Zeitlin L, Kim D, Working C, Johnson J, Bohorov O . Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail. Sci Transl Med. 2013; 5(199):199ra113. DOI: 10.1126/scitranslmed.3006608. View

Lewinsohn D, Swarbrick G, Cansler M, Null M, Rajaraman V, Frieder M . Human Mycobacterium tuberculosis CD8 T Cell Antigens/Epitopes Identified by a Proteomic Peptide Library. PLoS One. 2013; 8(6):e67016. PMC: 3689843. DOI: 10.1371/journal.pone.0067016. View

Lundegaard C, Lund O, Nielsen M . Accurate approximation method for prediction of class I MHC affinities for peptides of length 8, 10 and 11 using prediction tools trained on 9mers. Bioinformatics. 2008; 24(11):1397-8. DOI: 10.1093/bioinformatics/btn128. View

Wang H, Shi Y, Song J, Qi J, Lu G, Yan J . Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1. Cell. 2016; 164(1-2):258-268. PMC: 7111281. DOI: 10.1016/j.cell.2015.12.044. View

Lee J, Saphire E . Neutralizing ebolavirus: structural insights into the envelope glycoprotein and antibodies targeted against it. Curr Opin Struct Biol. 2009; 19(4):408-17. PMC: 2759674. DOI: 10.1016/j.sbi.2009.05.004. View

Dahlke C, Lunemann S, Kasonta R, Kreuels B, Schmiedel S, Ly M . Comprehensive Characterization of Cellular Immune Responses Following Ebola Virus Infection. J Infect Dis. 2016; 215(2):287-292. DOI: 10.1093/infdis/jiw508. View

Borthwick N, Lin Z, Akahoshi T, Llano A, Silva-Arrieta S, Ahmed T . Novel, in-natural-infection subdominant HIV-1 CD8+ T-cell epitopes revealed in human recipients of conserved-region T-cell vaccines. PLoS One. 2017; 12(4):e0176418. PMC: 5407754. DOI: 10.1371/journal.pone.0176418. View

Krissinel E, Henrick K . Inference of macromolecular assemblies from crystalline state. J Mol Biol. 2007; 372(3):774-97. DOI: 10.1016/j.jmb.2007.05.022. View

Gras S, Kedzierski L, Valkenburg S, Laurie K, Liu Y, Denholm J . Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proc Natl Acad Sci U S A. 2010; 107(28):12599-604. PMC: 2906563. DOI: 10.1073/pnas.1007270107. View

10.

Dikhit M, Kumar S, Vijaymahantesh , Sahoo B, Mansuri R, Amit A . Computational elucidation of potential antigenic CTL epitopes in Ebola virus. Infect Genet Evol. 2015; 36:369-375. DOI: 10.1016/j.meegid.2015.10.012. View

11.

Soria-Guerra R, Nieto-Gomez R, Govea-Alonso D, Rosales-Mendoza S . An overview of bioinformatics tools for epitope prediction: implications on vaccine development. J Biomed Inform. 2014; 53:405-14. DOI: 10.1016/j.jbi.2014.11.003. View

12.

Wu C, Zanker D, Valkenburg S, Tan B, Kedzierska K, Zou Q . Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals. Proc Natl Acad Sci U S A. 2011; 108(22):9178-83. PMC: 3107317. DOI: 10.1073/pnas.1105624108. View

13.

Theaker S, Rius C, Greenshields-Watson A, Lloyd A, Trimby A, Fuller A . T-cell libraries allow simple parallel generation of multiple peptide-specific human T-cell clones. J Immunol Methods. 2016; 430:43-50. PMC: 4783706. DOI: 10.1016/j.jim.2016.01.014. View

14.

Hoof I, Peters B, Sidney J, Pedersen L, Sette A, Lund O . NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics. 2008; 61(1):1-13. PMC: 3319061. DOI: 10.1007/s00251-008-0341-z. View

15.

Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti J . Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014; 514(7520):47-53. PMC: 4214273. DOI: 10.1038/nature13777. View

16.

Milligan I, Gibani M, Sewell R, Clutterbuck E, Campbell D, Plested E . Safety and Immunogenicity of Novel Adenovirus Type 26- and Modified Vaccinia Ankara-Vectored Ebola Vaccines: A Randomized Clinical Trial. JAMA. 2016; 315(15):1610-23. DOI: 10.1001/jama.2016.4218. View

17.

McElroy A, Akondy R, Davis C, Ellebedy A, Mehta A, Kraft C . Human Ebola virus infection results in substantial immune activation. Proc Natl Acad Sci U S A. 2015; 112(15):4719-24. PMC: 4403189. DOI: 10.1073/pnas.1502619112. View

18.

Gire S, Goba A, Andersen K, Sealfon R, Park D, Kanneh L . Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014; 345(6202):1369-72. PMC: 4431643. DOI: 10.1126/science.1259657. View

19.

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

20.

Nemat-Gorgani N, Guethlein L, Henn B, Norberg S, Chiaroni J, Sikora M . Diversity of KIR, HLA Class I, and Their Interactions in Seven Populations of Sub-Saharan Africans. J Immunol. 2019; 202(9):2636-2647. PMC: 6690726. DOI: 10.4049/jimmunol.1801586. View