About: Evaluation of T-activated proteins as recall antigens to monitor Epstein–Barr virus and human cytomegalovirus-specific T cells in a clinical trial setting

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About: Evaluation of T-activated proteins as recall antigens to monitor Epstein–Barr virus and human cytomegalovirus-specific T cells in a clinical trial setting Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Evaluation of T-activated proteins as recall antigens to monitor Epstein–Barr virus and human cytomegalovirus-specific T cells in a clinical trial setting
Creator	Protzer, Ulrike Bauer, Tanja Behrends, Uta Körber, Nina
topic	covid:ec5a93e3f998b8ae92dcd921af7cc792f812c608#this
source	PMC
abstract	BACKGROUND: Pools of overlapping synthetic peptides are routinely used for ex vivo monitoring of antigen-specific T-cell responses. However, it is rather unlikely that these peptides match those resulting from naturally processed antigens. T-activated proteins have been described as immunogenic and more natural stimulants, since they have to pass through antigen processing and comprise activation of all clinically relevant effector cell populations. METHODS: We performed comparative analysis of numbers and cytokine expression pattern of CD4 and CD8 T cells after stimulation with recombinant, urea-formulated T-activated EBV-BZLF1, -EBNA3A, and HCMV-IE1, and -pp65 proteins or corresponding overlapping peptide pools. Freshly isolated and cryopreserved PBMC of 30 EBV- and 19 HCMV-seropositive and seven EBV- and HCMV-seronegative subjects were stimulated ex vivo and analysed for IFN-γ, TNF and IL-2 production by flow cytometry-based intracellular cytokine staining. RESULTS: T-activated proteins showed a high specificity of 100% (EBV-BZLF1, HCMV-IE1, and -pp65) and 86% (EBV-EBNA3A), and a high T-cell stimulatory capacity of 73–95% and 67–95% using freshly isolated and cryopreserved PBMC, respectively. The overall CD4 T-cell response rates in both cohorts were comparable after stimulation with either T-activated protein or peptide pools with the exception of lower numbers of CD8 T cells detected after stimulation with T-activated EBV-EBNA3A- (p = 0.038) and HCMV-pp65- (p = 0.0006). Overall, the number of detectable antigen-specific T cells varied strongly between individuals. Cytokine expression patterns in response to T-activated protein and peptide pool-based stimulation were similar for CD4, but significantly different for CD8 T-cell responses. CONCLUSION: EBV and HCMV-derived T-activated proteins represent innovative, highly specific recall antigens suitable for use in immunological endpoint assays to evaluate success or failure in immunotherapy clinical trials (e.g. to assess the risk of EBV and/or HCMV reactivation after allogenic hematopoietic stem cell transplantation). T-activated proteins could be of particular importance, if an impaired antigen processing (e.g. in a post-transplant setting) must be taken into account.
has issue date	2020-06-17(xsd:dateTime)
bibo:doi	10.1186/s12967-020-02385-x
has license	cc-by
sha1sum (hex)	ec5a93e3f998b8ae92dcd921af7cc792f812c608
schema:url	https://doi.org/10.1186/s12967-020-02385-x
resource representing a document's title	Evaluation of T-activated proteins as recall antigens to monitor Epstein–Barr virus and human cytomegalovirus-specific T cells in a clinical trial setting
has PubMed Central identifier	PMC7298696
schema:publication	J Transl Med
resource representing a document's body	covid:ec5a93e3f998b8ae92dcd921af7cc792f812c608#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/ec5a93e3f998b8ae92dcd921af7cc792f812c608
is schema:about of	named entity 'However' named entity 'clinical trial' named entity 'T-CELL' named entity 'MONITORING' named entity 'RESULTING FROM' named entity 'COMPRISE' named entity 'BACKGROUND' named entity 'OVERLAPPING' named entity 'naturally' named entity 'effector cell' named entity 'natural' named entity 'stimulants' named entity 'responses' named entity 'Epstein-Barr' named entity 'antigen processing' named entity 'effector cell' named entity 'immunogenic' named entity 'antigens' named entity 'Epstein-Barr virus' named entity 'clinical trial' named entity 'peptides' named entity 'PBMC' named entity 'specific immunity' named entity 'IFN-γ' named entity 'BZLF1' named entity 'Germany' named entity 'HCMV' named entity 'HCMV' named entity 'EBV' named entity 'antigen' named entity 'seropositive' named entity 'HCMV' named entity 'HCMV' named entity 'EBV' named entity 'HCMV' named entity 'EBV' named entity 'NIH' named entity 'viral antigens' named entity 'T-cell' named entity 'IgM' named entity 'Denmark' named entity 'epitope mapping' named entity '5.00' named entity 'HCMV' named entity 'patient cohorts' named entity 'antigen' named entity 'peptides' named entity 'antigen' named entity 'Lophius' named entity 'cryopreserved' named entity 'EBV' named entity 'transplant recipients' named entity 'EBV' named entity 'PBMC' named entity 'antigen' named entity 'BZLF1' named entity 'BZLF1' named entity 'CD8 T-cell' named entity 'Becton-Dickinson' named entity 'cytokine' named entity 'cryopreserved' named entity 'antigen processing' named entity 'stimulant' named entity 'streptomycin' named entity 'IFN-γ' named entity 'immunosuppressive therapy' named entity 'background subtraction' named entity 'CD4' named entity 'PBMC' named entity 'HCMV' named entity 'CD8 T cells' named entity 'quality control' named entity 'Denmark' named entity 'EBV' named entity 'T-cell' named entity 'standard operating procedure' named entity 'negative control' named entity 'patient cohorts'

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