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

Jonathan Powlson,Daniel Wright,Antra Zeltina,Mark Giza,Morten Nielsen,Tommy Rampling,Navin Venkatrakaman,Thomas A Bowden,Adrian V.S Hill,Katie J Ewer

doi:10.1016/j.celrep.2019.10.105

Jonathan Powlson, Daniel Wright + Show 8 more

Open Access

https://doi.org/10.1016/j.celrep.2019.10.105

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Abstract

SummaryEbolavirus 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.

Highlights

The West African Ebolavirus epidemic that began in Guinea in December 2013 claimed more than 11,000 lives, eclipsing all previously recorded outbreaks combined (WHO, 2017; Baize et al, 2014)
We have previously reported a clinical trial in which volunteers were primed with a monovalent chimpanzee adenovirus encoding the EBOV GP gene (Ewer et al, 2016)
ELISPOT Responses to Pooled Peptides As part of the immunomonitoring performed during the previously reported clinical trial (Ewer et al, 2016), freshly isolated Peripheral blood mononuclear cells (PBMCs) collected 7 days after boosting with MVA were assayed against 10 pools of overlapping peptides spanning the length of the vaccine antigen insert, which includes a signal peptide and the GP1 and GP2 subunits

Summary

Introduction

The West African Ebolavirus epidemic that began in Guinea in December 2013 claimed more than 11,000 lives, eclipsing all previously recorded outbreaks combined (WHO, 2017; Baize et al, 2014). The etiological agent of this outbreak, Zaire ebolavirus (EBOV), is one of five species within the Ebolavirus genus of the Filoviridae family (Kuhn et al, 2010). Three other members of this genus, Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV), and Bundibugyo ebolavirus (BDBV), are pathogenic in humans (Feldmann and Geisbert, 2011). The case fatality rate of the West African epidemic (2013–2016) was estimated at 40%, it has been as high as 90% in previous outbreaks (WHO, 2017). Despite the threat that EBOV and other filoviruses pose, relatively little is known about the cellular immune response to filoviruses in humans

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