Identification and characterisation of conserved epitopes of E. ruminantium that activate Th1 CD4+ T cells : towards the development of a multi-epitope vaccine

dc.contributor.authorThema, Nontobeko
dc.contributor.authorTshilwane, Selaelo Ivy
dc.contributor.authorPretorius, Alri
dc.contributor.authorSon, L.
dc.contributor.authorSmith, R.M.
dc.contributor.authorSteyn, Helena C.
dc.contributor.authorLiebenberg, Junita
dc.contributor.authorVan Kleef, Mirinda
dc.date.accessioned2019-03-13T11:28:50Z
dc.date.issued2019-03
dc.description.abstractSeveral studies have shown that cytotoxic T lymphocytes (CTL) require CD4 + Th1 epitopes to generate strong immune responses to intracellular pathogens. However, not much is known about Ehrlichia ruminantium epitopes, particularly those that can be considered potential candidates for inclusion in a multi-epitope vaccine. In order to identify CD4+ Th1 epitopes that induce IFNγ, a number of proteins previously identified as immunogenic were first screened to determine if they induce cellular immunity in tick infected immune sheep PBMC. Significant IFN-γ production and other Th1 cytokines were evident for 10 recombinant proteins in all sheep tested. Secondly, peptides (n = 246) derived from the top 10 E. ruminantium vaccine candidate proteins were assayed using enzyme linked immunospot (ELISPOT) assay, quantitative real-time PCR and flow cytometry. Of the 246 peptides, 23 peptides, Erum0660 (p0660-42), Erum1150 (p1150-18, p1150-19), Erum2540 (p2540-6, p2540-16, p2540-19, p2540-20, p2540-21), Erum5420 (p5420-13, p5420-14), Erum7140 (p7140-6, p7140-7, p7140-12, p7140-13, p7140-20), Erum7320 (p7320-8, p7320-9, p7320-21), Erum7350 (p7350-9), Erum7360 (p7360-8), Erum7620 (p7620-2, p7620-12) and Erum8010 (p8010-8) were identified that stimulate the best and different cell mediated immune responses. Amino acid sequences of these peptides except for p7140-12, p7140-13, p7140-20, and p7350-9 were conserved between 13 different local strains. These peptides could efficiently induce memory CD4+ T cells to rapidly proliferate and significantly increase IFN-γ production in immune sheep PBMC. The upregulation of pro-inflammatory cytokines, which include, IL-1α, IL-2, IL-12p40, TNF-α, IFN-γ, inducible nitric oxide synthase (iNOS) and granulocyte-macrophage colony stimulating factor (GM-CSF) was also detected. Our results show that these peptides could serve as promising candidates for a multi-epitope vaccine against E. ruminantium.en_ZA
dc.description.departmentVeterinary Tropical Diseasesen_ZA
dc.description.embargo2020-03-01
dc.description.librarianhj2019en_ZA
dc.description.sponsorshipThe NRF, THRIP, and RMRD-SA in collaboration with OBP and Economic Competitiveness Support Programme and the ARC-OVR, South Africa.en_ZA
dc.description.urihttp://www.elsevier.com/locate/molimmen_ZA
dc.identifier.citationThema, N., Tshilwane, S.I., Pretorius, A. et al. 2019, 'Identification and characterisation of conserved epitopes of E. ruminantium that activate Th1 CD4+ T cells : towards the development of a multi-epitope vaccine', Molecular Immunology, vol. 107, pp. 106-114.en_ZA
dc.identifier.issn0161-5890 (print)
dc.identifier.issn1872-9142 (online)
dc.identifier.other10.1016/j.molimm.2018.12.012
dc.identifier.urihttp://hdl.handle.net/2263/68643
dc.language.isoenen_ZA
dc.publisherElsevieren_ZA
dc.rights© 2018 Elsevier Ltd. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Molecular Immunology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Molecular Immunology, vol. 107, pp. 106-114, 2019. doi : 10.1016/j.molimm.2018.12.012.en_ZA
dc.subjectCytotoxic T lymphocytes (CTL)en_ZA
dc.subjectEnzyme linked immunospot (ELISPOT)en_ZA
dc.subjectEhrlichia ruminantiumen_ZA
dc.subjectAntigensen_ZA
dc.subjectCD4+T cellsen_ZA
dc.subjectPeptidesen_ZA
dc.subjectInterferon gamma (IFNγ)en_ZA
dc.titleIdentification and characterisation of conserved epitopes of E. ruminantium that activate Th1 CD4+ T cells : towards the development of a multi-epitope vaccineen_ZA
dc.typePostprint Articleen_ZA

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