Characterisation of the T-cell Response to Ebola Virus Glycoprotein Amongst Survivors of the 2013-16 West Africa Epidemic

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Feb 20

PMID 33608536

Citations 8

Authors

T R W Tipton

Y Hall

J A Bore

A White

L S Sibley

C Sarfas

Y Yuki

M Martin

S Longet

J Mellors

K Ewer

S Gunther

M Carrington

M K Konde

M W Carroll

Affiliations

Soon will be listed here.

Abstract

Zaire ebolavirus (EBOV) is a highly pathogenic filovirus which can result in Ebola virus disease (EVD); a serious medical condition that presents as flu like symptoms but then often leads to more serious or fatal outcomes. The 2013-16 West Africa epidemic saw an unparalleled number of cases. Here we show characterisation and identification of T cell epitopes in surviving patients from Guinea to the EBOV glycoprotein. We perform interferon gamma (IFNγ) ELISpot using a glycoprotein peptide library to identify T cell epitopes and determine the CD4 or CD8 T cell component response. Additionally, we generate data on the T cell phenotype and measure polyfunctional cytokine secretion by these antigen specific cells. We show candidate peptides able to elicit a T cell response in EBOV survivors and provide inferred human leukocyte antigen (HLA) allele restriction. This data informs on the long-term T cell response to Ebola virus disease and highlights potentially important immunodominant peptides.

Citing Articles

Rational design of next-generation filovirus vaccines with glycoprotein stabilization, nanoparticle display, and glycan modification.

Lee Y, Zhang Y, Newby M, Ward G, Gomes K, Auclair S bioRxiv. 2025; .

PMID: 40060701 PMC: 11888476. DOI: 10.1101/2025.03.02.641072.

Using minor variant genomes and machine learning to study the genome biology of SARS-CoV-2 over time.

Dong X, Matthews D, Gallo G, Darby A, Donovan-Banfield I, Goldswain H Nucleic Acids Res. 2025; 53(4).

PMID: 39970290 PMC: 11838042. DOI: 10.1093/nar/gkaf077.

Early B-cell development and B-cell maturation are impaired in patients with active hemophagocytic lymphohistiocytosis.

Shim J, Park S, Venkateswaran S, Kumar D, Prince C, Parihar V Blood. 2023; 142(23):1972-1984.

PMID: 37624902 PMC: 10731577. DOI: 10.1182/blood.2023020426.

T-Cell Immunity in COVID-19-Recovered Individuals and Individuals Vaccinated with the Combined Vector Vaccine Gam-COVID-Vac.

Krechetov S, Vtorushina V, Inviyaeva E, Gorodnova E, Kolesnik S, Kudlay D Int J Mol Sci. 2023; 24(3).

PMID: 36768254 PMC: 9916700. DOI: 10.3390/ijms24031930.

RNA Viruses, Pregnancy and Vaccination: Emerging Lessons from COVID-19 and Ebola Virus Disease.

Dhanya C, Shailaja A, Mary A, Kandiyil S, Savithri A, Lathakumari V Pathogens. 2022; 11(7).

PMID: 35890044 PMC: 9322689. DOI: 10.3390/pathogens11070800.

References

Zhou Y, Sullivan N . Immunology and evolvement of the adenovirus prime, MVA boost Ebola virus vaccine. Curr Opin Immunol. 2015; 35:131-6. DOI: 10.1016/j.coi.2015.06.006. View

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

Henao-Restrepo A, Camacho A, Longini I, Watson C, Edmunds W, Egger M . Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2016; 389(10068):505-518. PMC: 5364328. DOI: 10.1016/S0140-6736(16)32621-6. View

Thom R, Tipton T, Strecker T, Hall Y, Bore J, Maes P . Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study. Lancet Infect Dis. 2020; 21(4):507-516. PMC: 7553754. DOI: 10.1016/S1473-3099(20)30736-2. View

Compeer E, Flinsenberg T, van der Grein S, Boes M . Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation. Front Immunol. 2012; 3:37. PMC: 3342355. DOI: 10.3389/fimmu.2012.00037. View

Sakabe S, Sullivan B, Hartnett J, Robles-Sikisaka R, Gangavarapu K, Cubitt B . Analysis of CD8 T cell response during the 2013-2016 Ebola epidemic in West Africa. Proc Natl Acad Sci U S A. 2018; 115(32):E7578-E7586. PMC: 6094108. DOI: 10.1073/pnas.1806200115. View

Halperin S, Das R, Onorato M, Liu K, Martin J, Grant-Klein R . Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults. J Infect Dis. 2019; 220(7):1127-1135. PMC: 6812306. DOI: 10.1093/infdis/jiz241. View

Ahmad B, Ashfaq U, Rahman M, Masoud M, Zubair Yousaf M . Conserved B and T cell epitopes prediction of ebola virus glycoprotein for vaccine development: An immuno-informatics approach. Microb Pathog. 2019; 132:243-253. PMC: 7270928. DOI: 10.1016/j.micpath.2019.05.010. View

Wykes M, Renia L . ELISPOT Assay to Measure Peptide-specific IFN-γ Production. Bio Protoc. 2021; 7(11):e2302. PMC: 8410284. DOI: 10.21769/BioProtoc.2302. View

10.

Agrati C, Castilletti C, Casetti R, Sacchi A, Falasca L, Turchi F . Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection. Cell Death Dis. 2016; 7:e2164. PMC: 4823956. DOI: 10.1038/cddis.2016.55. View

11.

Ledgerwood J, Costner P, Desai N, Holman L, Enama M, Yamshchikov G . A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine. 2010; 29(2):304-13. DOI: 10.1016/j.vaccine.2010.10.037. View

12.

Francica J, Varela-Rohena A, Medvec A, Plesa G, Riley J, Bates P . Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein. PLoS Pathog. 2010; 6(9):e1001098. PMC: 2936550. DOI: 10.1371/journal.ppat.1001098. View

13.

Olinger G, Bailey M, Dye J, Bakken R, Kuehne A, Kondig J . Protective cytotoxic T-cell responses induced by venezuelan equine encephalitis virus replicons expressing Ebola virus proteins. J Virol. 2005; 79(22):14189-96. PMC: 1280180. DOI: 10.1128/JVI.79.22.14189-14196.2005. View

14.

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

15.

Gattinoni L, Speiser D, Lichterfeld M, Bonini C . T memory stem cells in health and disease. Nat Med. 2017; 23(1):18-27. PMC: 6354775. DOI: 10.1038/nm.4241. View

16.

Powlson J, Wright D, Zeltina A, Giza M, Nielsen M, Rampling T . Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus. Cell Rep. 2019; 29(9):2537-2545.e3. PMC: 6899439. DOI: 10.1016/j.celrep.2019.10.105. View

17.

Ewer K, OHara G, Duncan C, Collins K, Sheehy S, Reyes-Sandoval A . Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun. 2013; 4:2836. PMC: 3868203. DOI: 10.1038/ncomms3836. View

18.

Ford T, Wenden C, Mbekeani A, Dally L, Cox J, Morin M . Cryopreservation-related loss of antigen-specific IFNγ producing CD4 T-cells can skew immunogenicity data in vaccine trials: Lessons from a malaria vaccine trial substudy. Vaccine. 2017; 35(15):1898-1906. PMC: 5387668. DOI: 10.1016/j.vaccine.2017.02.038. View

19.

Stanley D, Honko A, Asiedu C, Trefry J, Lau-Kilby A, Johnson J . Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge. Nat Med. 2014; 20(10):1126-9. DOI: 10.1038/nm.3702. View

20.

Marzi A, Engelmann F, Feldmann F, Haberthur K, Shupert W, Brining D . Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates. Proc Natl Acad Sci U S A. 2013; 110(5):1893-8. PMC: 3562844. DOI: 10.1073/pnas.1209591110. View