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Article ; Online: Bioinformatic and Experimental Analysis of T Cell Immune Reactivity to SARS-CoV-2 and its Variants.

Tarke, Alison / Grifoni, Alba / Sette, Alessandro

Frontiers in bioinformatics

2022 Volume 2, Page(s) 876380

Abstract: Definition of the T cells responses to SARS-CoV-2 and associated variants is critical to understanding the complexity of adaptive immunity against SARS-CoV-2 infection. Several groups have investigated the T cells responses by both experimental and ... ...

Abstract	Definition of the T cells responses to SARS-CoV-2 and associated variants is critical to understanding the complexity of adaptive immunity against SARS-CoV-2 infection. Several groups have investigated the T cells responses by both experimental and bioinformatical approaches. Here we summarize recent findings on CD4 and CD8 T cell responses to SARS-CoV-2 with particular emphasis on emerging variants of concern, consolidating the results on the impact of SARS-CoV-2 variants on T cell responses by performing an additional metanalysis emphasizing the lower impact of variant mutations in dominant T cell epitopes. The consensus is that the majority of T cell responses are conserved across all current SARS-CoV-2 variants, including Delta and Omicron. Thus, even in concomitance with reduced antibody and B cell responses, T cells can still provide a second line of antiviral immunity.
Language	English
Publishing date	2022-05-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2673-7647
ISSN (online)	2673-7647
DOI	10.3389/fbinf.2022.876380
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Bioinformatic and Experimental Analysis of T Cell Immune Reactivity to SARS-CoV-2 and its Variants

Alison Tarke / Alba Grifoni / Alessandro Sette

Frontiers in Bioinformatics, Vol

2022 Volume 2

Abstract	Definition of the T cells responses to SARS-CoV-2 and associated variants is critical to understanding the complexity of adaptive immunity against SARS-CoV-2 infection. Several groups have investigated the T cells responses by both experimental and bioinformatical approaches. Here we summarize recent findings on CD4 and CD8 T cell responses to SARS-CoV-2 with particular emphasis on emerging variants of concern, consolidating the results on the impact of SARS-CoV-2 variants on T cell responses by performing an additional metanalysis emphasizing the lower impact of variant mutations in dominant T cell epitopes. The consensus is that the majority of T cell responses are conserved across all current SARS-CoV-2 variants, including Delta and Omicron. Thus, even in concomitance with reduced antibody and B cell responses, T cells can still provide a second line of antiviral immunity.
Keywords	SARS-CoV-2 ; T cells ; variants ; epitopes ; vaccination ; Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	570
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Tumor-specific T cell-mediated upregulation of PD-L1 in myelodysplastic syndrome cells does not affect T-cell killing.

Ferrari, Valentina / Tarke, Alison / Fields, Hannah / Tanaka, Tiffany N / Searles, Stephen / Zanetti, Maurizio

Frontiers in oncology

2022 Volume 12, Page(s) 915629

Abstract: The PD-1:PD-L1 axis is a binary interaction that delivers inhibitory signals to T cells, impeding both immune surveillance and response to immunotherapy. Here we analyzed a phenomenon whereby tumor-specific T cells induce PD-L1 upregulation in autologous ...

Abstract	The PD-1:PD-L1 axis is a binary interaction that delivers inhibitory signals to T cells, impeding both immune surveillance and response to immunotherapy. Here we analyzed a phenomenon whereby tumor-specific T cells induce PD-L1 upregulation in autologous MDS cells in short-term culture, through a mechanism that is cell-contact-independent and partially IFNγ-dependent. After investigating a panel of small-molecule inhibitors, we determined that PD-L1 upregulation was attributed to the PKR-like ER kinase (PERK) branch of the unfolded protein response. Interestingly, we found that the cytotoxic capacity of tumor-specific T cells was not impaired by the expression of PD-L1 on MDS target cells. These results highlight a little appreciated aspect of PD-1:PD-L1 regulation in hematologic cancers and indicate that this phenomenon, while likely to hinder autochthonous immune surveillance, may not be an obstacle to immunotherapies such as personalized adoptive T-cell therapy.
Language	English
Publishing date	2022-08-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.915629
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Article ; Online: PopCover-2.0. Improved Selection of Peptide Sets With Optimal HLA and Pathogen Diversity Coverage.

Nilsson, Jonas Birkelund / Grifoni, Alba / Tarke, Alison / Sette, Alessandro / Nielsen, Morten

Frontiers in immunology

2021 Volume 12, Page(s) 728936

Abstract: The use of minimal peptide sets offers an appealing alternative for design of vaccines and T cell diagnostics compared to conventional whole protein approaches. T cell immunogenicity towards peptides is contingent on binding to human leukocyte antigen ( ... ...

Abstract	The use of minimal peptide sets offers an appealing alternative for design of vaccines and T cell diagnostics compared to conventional whole protein approaches. T cell immunogenicity towards peptides is contingent on binding to human leukocyte antigen (HLA) molecules of the given individual. HLA is highly polymorphic, and each variant typically presents a different repertoire of peptides. This polymorphism combined with pathogen diversity challenges the rational selection of peptide sets with broad immunogenic potential and population coverage. Here we propose PopCover-2.0, a simple yet highly effective method, for resolving this challenge. The method takes as input a set of (predicted) CD8 and/or CD4 T cell epitopes with associated HLA restriction and pathogen strain annotation together with information on HLA allele frequencies, and identifies peptide sets with optimal pathogen and HLA (class I and II) coverage. PopCover-2.0 was benchmarked on historic data in the context of HIV and SARS-CoV-2. Further, the immunogenicity of the selected SARS-CoV-2 peptides was confirmed by experimentally validating the peptide pools for T cell responses in a panel of SARS-CoV-2 infected individuals. In summary, PopCover-2.0 is an effective method for rational selection of peptide subsets with broad HLA and pathogen coverage. The tool is available at https://services.healthtech.dtu.dk/service.php?PopCover-2.0.
MeSH term(s)	Alleles ; Allergy and Immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; Epitopes, T-Lymphocyte/immunology ; Genotype ; HLA Antigens/classification ; HLA Antigens/genetics ; HLA Antigens/immunology ; Humans ; Immunogenicity, Vaccine ; Immunologic Techniques ; Peptides/classification ; Peptides/immunology ; SARS-CoV-2/immunology
Chemical Substances	Epitopes, T-Lymphocyte ; HLA Antigens ; Peptides
Language	English
Publishing date	2021-08-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.728936
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Targets and cross-reactivity of human T cell recognition of Common Cold Coronaviruses.

Tarke, Alison / Zhang, Yun / Methot, Nils / Narowski, Tara M / Phillips, Elizabeth / Mallal, Simon / Frazier, April / Filaci, Gilberto / Weiskopf, Daniela / Dan, Jennifer M / Premkumar, Lakshmanane / Scheuermann, Richard H / Sette, Alessandro / Grifoni, Alba

bioRxiv : the preprint server for biology

2023

Abstract: The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, ... ...

Abstract	The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, including sarbecoCoV (SARS-CoV and SARS-CoV-2) and merbecoCoV (MERS-CoV). It is therefore warranted to explore pan-CoV vaccine concepts, to provide adaptive immune protection against new potential CoV outbreaks, particularly in the context of betaCoV sub lineages. To explore the feasibility of eliciting CD4
Language	English
Publishing date	2023-01-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.04.522794
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Targets and cross-reactivity of human T cell recognition of common cold coronaviruses.

Cell reports. Medicine

2023 Volume 4, Issue 6, Page(s) 101088

Abstract: The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and ... ...

Abstract	The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and Beta (OC43) common cold CoVs (CCCs) in pre-pandemic samples. S, N, M, and nsp3 antigens are immunodominant, as shown for severe acute respiratory syndrome 2 (SARS2), while nsp2 and nsp12 are Alpha or Beta specific. We further identify 78 OC43- and 87 NL63-specific epitopes, and, for a subset of those, we assess the T cell capability to cross-recognize sequences from representative viruses belonging to AlphaCoV, sarbecoCoV, and Beta-non-sarbecoCoV groups. We find T cell cross-reactivity within the Alpha and Beta groups, in 89% of the instances associated with sequence conservation >67%. However, despite conservation, limited cross-reactivity is observed for sarbecoCoV, indicating that previous CoV exposure is a contributing factor in determining cross-reactivity. Overall, these results provide critical insights in developing future pan-CoV vaccines.
MeSH term(s)	Humans ; Common Cold ; T-Lymphocytes ; COVID-19 ; SARS-CoV-2 ; Cross Reactions
Language	English
Publishing date	2023-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.101088
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Article ; Online: Defining antigen targets to dissect vaccinia virus and monkeypox virus-specific T cell responses in humans.

Grifoni, Alba / Zhang, Yun / Tarke, Alison / Sidney, John / Rubiro, Paul / Reina-Campos, Maria / Filaci, Gilberto / Dan, Jennifer M / Scheuermann, Richard H / Sette, Alessandro

Cell host & microbe

2022 Volume 30, Issue 12, Page(s) 1662–1670.e4

Abstract: The monkeypox virus (MPXV) outbreak confirmed in May 2022 in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is known regarding MPXV immunity in the context of MPXV infection or vaccination with ... ...

Abstract	The monkeypox virus (MPXV) outbreak confirmed in May 2022 in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is known regarding MPXV immunity in the context of MPXV infection or vaccination with vaccinia-based vaccines (VACV). As with vaccinia, T cells are likely to provide an important contribution to overall immunity to MPXV. Here, we leveraged the epitope information available in the Immune Epitope Database (IEDB) on VACV to predict potential MPXV targets recognized by CD4
MeSH term(s)	Humans ; Vaccinia virus ; Monkeypox virus/physiology ; Vaccinia ; Mpox (monkeypox) ; Epitopes
Chemical Substances	Epitopes
Language	English
Publishing date	2022-12-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2022.11.003
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Article: Mpox vaccine and infection-driven human immune signatures.

Cohn, Hallie / Bloom, Nathaniel / Cai, Gianna / Clark, Jordan / Tarke, Alison / Bermúdez-González, Maria C / Altman, Deena / Lugo, Luz Amarilis / Lobo, Francisco Pereira / Marquez, Susanna / Chen, Jin-Qiu / Ren, Wenlin / Qin, Lili / Crotty, Shane / Krammer, Florian / Grifoni, Alba / Sette, Alessandro / Simon, Viviana / Coelho, Camila H

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS ... ...

Abstract	Background: Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side effects than previous smallpox vaccines and demonstrated efficacy against mpox infection in humans. Comparing JYNNEOS vaccine- and mpox-induced immunity is imperative to evaluate JYNNEOS' immunogenicity and inform vaccine administration and design. Methods: We examined the polyclonal serum (ELISA) and single B cell (heavy chain gene and transcriptome data) antibody repertoires and T cells (AIM and ICS assays) induced by the JYNNEOS vaccine as well as mpox infection. Findings: Gene-level plasmablast and antibody responses were negligible and JYNNEOS vaccinee sera displayed minimal binding to recombinant mpox proteins and native proteins from the 2022 outbreak strain. In contrast, recent mpox infection (within 20-102 days) induced robust serum antibody responses to A29L, A35R, A33R, B18R, and A30L, and to native mpox proteins, compared to vaccinees. JYNNEOS vaccine recipients presented comparable CD4 and CD8 T cell responses against orthopox peptides to those observed after mpox infection. Interpretation: JYNNEOS immunization does not elicit a robust B cell response, and its immunogenicity may be mediated by T cells. Funding: Research reported in this publication was supported, in part, by the National Cancer Institute of the National Institutes of Health under Award Number U54CA267776, U19AI168631(VS), as well as institutional funds from the Icahn School of Medicine.
Language	English
Publishing date	2023-03-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.07.23286701
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Article ; Online: Early and Polyantigenic CD4 T Cell Responses Correlate with Mild Disease in Acute COVID-19 Donors.

Tarke, Alison / Potesta, Marina / Varchetta, Stefania / Fenoglio, Daniela / Iannetta, Marco / Sarmati, Loredana / Mele, Dalila / Dentone, Chiara / Bassetti, Matteo / Montesano, Carla / Mondelli, Mario U / Filaci, Gilberto / Grifoni, Alba / Sette, Alessandro

International journal of molecular sciences

2022 Volume 23, Issue 13

Abstract: We assessed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in samples from 89 acute COVID-19 patients, utilizing blood samples collected during the first wave of COVID-19 in Italy. The goal of the study was to examine correlations between SARS-CoV-2- ... ...

Abstract	We assessed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in samples from 89 acute COVID-19 patients, utilizing blood samples collected during the first wave of COVID-19 in Italy. The goal of the study was to examine correlations between SARS-CoV-2-specific T cell responses in the early phase comparing mild, moderate, or severe COVID-19 disease outcomes. T cell responses to the spike (S) and non-S proteins were measured in a combined activation-induced marker (AIM) and intracellular cytokine staining (ICS) assay. Early CD4+ T cell responses to SARS-CoV-2 S correlated with milder disease by both AIM and IFNγ ICS readouts. The correlation of S-specific CD4+ T cell responses with milder disease severity was most striking within the first two weeks of symptom onset compared to later time points. Furthermore, donors with milder disease were associated with polyantigenic CD4+ T cell responses that recognized more prominently non-S proteins in addition to S, while severe acute COVID-19 was characterized by lower magnitudes of CD4+ T cell responses and a narrower repertoire. In conclusion, this study highlights that both the magnitude and breadth of early SARS-CoV-2-specific CD4+ T cell responses correlated with milder disease outcomes in acute COVID-19 patients.
MeSH term(s)	CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; COVID-19 ; Humans ; Italy ; SARS-CoV-2
Language	English
Publishing date	2022-06-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23137155
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Article: Humoral and cellular immune memory to four COVID-19 vaccines.

Zhang, Zeli / Mateus, Jose / Coelho, Camila H / Dan, Jennifer M / Moderbacher, Carolyn Rydyznski / Gálvez, Rosa Isela / Cortes, Fernanda H / Grifoni, Alba / Tarke, Alison / Chang, James / Escarrega, E Alexandar / Kim, Christina / Goodwin, Benjamin / Bloom, Nathaniel I / Frazier, April / Weiskopf, Daniela / Sette, Alessandro / Crotty, Shane

bioRxiv : the preprint server for biology

2022

Abstract: Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be ... ...

Abstract	Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4
Language	English
Publishing date	2022-03-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.03.18.484953
Database	MEDical Literature Analysis and Retrieval System OnLINE

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