المؤلفون: Hannah Voic, Xiuying Li, Jun-Ho Jang, Chunbin Zou, Prithu Sundd, Jonathan Alder, Mauricio Rojas, Divay Chandra, Scott Randell, Rama K. Mallampalli, Yohannes Tesfaigzi, Tyrone Ryba, Toru Nyunoya

المصدر: BMC Genomics, Vol 20, Iss 1, Pp 1-12 (2019)

مصطلحات موضوعية: Replicative senescence, Primary human bronchial epithelial cells, RNA-seq, Cigarette smoke, Biotechnology, TP248.13-248.65, Genetics, QH426-470

الوصف: Abstract Background Aging is affected by genetic and environmental factors, and cigarette smoking is strongly associated with accumulation of senescent cells. In this study, we wanted to identify genes that may potentially be beneficial for cell survival in response to cigarette smoke and thereby may contribute to development of cellular senescence. Results Primary human bronchial epithelial cells from five healthy donors were cultured, treated with or without 1.5% cigarette smoke extract (CSE) for 24 h or were passaged into replicative senescence. Transcriptome changes were monitored using RNA-seq in CSE and non-CSE exposed cells and those passaged into replicative senescence. We found that, among 1534 genes differentially regulated during senescence and 599 after CSE exposure, 243 were altered in both conditions, representing strong enrichment. Pathways and gene sets overrepresented in both conditions belonged to cellular processes that regulate reactive oxygen species, proteasome degradation, and NF-κB signaling. Conclusions Our results offer insights into gene expression responses during cellular aging and cigarette smoke exposure, and identify potential molecular pathways that are altered by cigarette smoke and may also promote airway epithelial cell senescence.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12864-018-5409-zTest; https://doaj.org/toc/1471-2164Test

الوصول الحر: https://doaj.org/article/c7aa9ac2c59a48a6934f46a03d353efdTest

المؤلفون: Alba Grifoni, Hannah Voic, Esther Dawen Yu, Jose Mateus, Kai Mei Yan Fung, Alice Wang, Grégory Seumois, Aruna D. De Silva, Rashika Tennekon, Sunil Premawansa, Gayani Premawansa, Rashmi Tippalagama, Ananda Wijewickrama, Ashu Chawla, Jason Greenbaum, Bjoern Peters, Vijayanand Pandurangan, Daniela Weiskopf, Alessandro Sette

المصدر: Vaccines, Vol 10, Iss 4, p 612 (2022)

مصطلحات موضوعية: CD8+ T cells, DENV, hemorrhagic disease, transcriptome, phenotypes, Medicine

الوصف: While several lines of evidence suggest a protective role of T cells against disease associated with Dengue virus (DENV) infection, their potential contribution to immunopathology in the acute phase of DENV infection remains controversial, and it has been hypothesized that the more severe form of the disease (dengue hemorrhagic fever, DHF) is associated with altered T cell responses. To address this question, we determined the transcriptomic profiles of DENV-specific CD8+ T cells in a cohort of 40 hospitalized dengue patients with either a milder form of the disease (dengue fever, DF) or a more severe disease form (dengue hemorrhagic fever, DHF). We found multiple transcriptomic signatures, one associated with DENV-specific interferon-gamma responding cells and two other gene signatures, one specifically associated with the acute phase and the other with the early convalescent phase. Additionally, we found no differences in quantity and quality of DENV-specific CD8+ T cells based on disease severity. Taken together with previous findings that did not detect altered DENV-specific CD4 T cell responses, the current analysis argues against alteration in DENV-specific T cell responses as being a correlate of immunopathology.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-393X/10/4/612Test; https://doaj.org/toc/2076-393XTest

الوصول الحر: https://doaj.org/article/97469ca26a384d278e732114634f117fTest

المؤلفون: Esther Dawen Yu, Alba Grifoni, Aaron Sutherland, Hannah Voic, Eric Wang, April Frazier, Natalia Jimenez-Truque, Sandra Yoder, Sabrina Welsh, Stacey Wooden, Wayne Koff, Buddy Creech, Alessandro Sette, Ricardo da Silva Antunes

المصدر: Vaccines, Vol 9, Iss 5, p 426 (2021)

مصطلحات موضوعية: T cells, protein immunodominance, cytokine polarization, influenza viruses, vaccine, Medicine

الوصف: The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax®, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins. CD4 T cell reactivity was mostly directed to HA/NA proteins in influenza B strains, and NP/M1/M2/NS1/NEP proteins in the case of the Influenza A strains. CD8 responses to both influenza A and B viruses preferentially targeted the more conserved core viral proteins. Following vaccination, both CD4 and CD8 responses against the various influenza antigens were increased in day 15 to day 91 post vaccination period, and maintained a Th1 polarized profile. Importantly, no vaccine interference was detected, with the increased responses balanced across all four included viral strains for both CD4 and CD8 T cells, and targeting HA and multiple additional viral antigens.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-393X/9/5/426Test; https://doaj.org/toc/2076-393XTest

الوصول الحر: https://doaj.org/article/adeb79b7d5194964b2eec16735ef5045Test

المؤلفون: Alba Grifoni, Eugene Moore, Hannah Voic, John Sidney, Elizabeth Phillips, Ramesh Jadi, Simon Mallal, Aruna D. De Silva, Aravinda M. De Silva, Bjoern Peters, Daniela Weiskopf, Alessandro Sette

المصدر: Frontiers in Immunology, Vol 10 (2019)

مصطلحات موضوعية: DENV, CD4+T cells, HLA-DP, HLA-DQ, HLA-DRB3/4/5, adaptive immunity, Immunologic diseases. Allergy, RC581-607

الوصف: Background: Dengue Virus (DENV) associated disease is a major public health problem. Assessment of HLA class II restricted DENV-specific responses is relevant for immunopathology and definition of correlates of protection. While previous studies characterized responses restricted by the HLA-DRB1 locus, the responses associated with other class II loci have not been characterized to date. Accordingly, we mapped HLA-DP, DQ, and DRB3/4/5 restricted DENV-specific CD4 T cell epitopes in PBMCs derived from the DENV endemic region Sri Lanka.Methods: We studied 12 DP, DQ, and DRB3/4/5 alleles that are commonly expressed and provide worldwide coverage >82% for each of the loci analyzed and >99% when combined. CD4+ T cells purified by negative selection were stimulated with pools of HLA-predicted binders for 2 weeks with autologous APC. Epitope reactive T cells were enumerated using IFNγ ELISPOT assay. This strategy was previously applied to identify DRB1 restricted epitopes. In parallel, membrane expression levels of HLA-DR, DP, and DQ proteins was assessed using flow cytometry.Results: Epitopes were identified for all DP, DQ, and DRB3/4/5 allelic variants albeit with magnitudes significantly lower than the ones previously observed for the DRB1 locus. This was in line with lower membrane expression of HLA-DP and DQ molecules on the PBMCs tested, as compared to HLA-DR. Significant differences between loci were observed in antigen immunodominance. Capsid responses were dominant for DRB1/3/4/5 and DP alleles but negligible for the DQ alleles. NS3 responses were dominant in the case of DRB1/3/4/5 and DQ but absent in the case of DP. NS1 responses were prominent in the case of the DP alleles, but negligible in the case of DR and DQ. In terms of epitope specificity, repertoire was largely overlapping between DRB1 and DRB3/4/5, while DP and DQ loci recognized largely distinct epitope sets.Conclusion: The HLA-DP, DQ, and DRB3/4/5 loci mediate DENV-CD4 specific immune responses of lower magnitude as compared to HLA-DRB1, consistent with their lower levels of expression. The responses are associated with distinct and characteristic patterns of immunodominance, and variable epitope overlap across loci.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fimmu.2019.01568/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/04e22b507b034ec6b6d751dc9b9140f0Test

المؤلفون: Jose Mateus, Alba Grifoni, Hannah Voic, Michael A. Angelo, Elizabeth Phillips, Simon Mallal, John Sidney, Alessandro Sette, Daniela Weiskopf

المصدر: Viruses, Vol 12, Iss 11, p 1300 (2020)

مصطلحات موضوعية: yellow fever virus, epitopes, CD4+ T cells, vaccination, T cells, Microbiology, QR1-502

الوصف: Yellow fever virus (YFV) is a mosquito-borne member of the genus flavivirus, including other important human-pathogenic viruses, such as dengue, Japanese encephalitis, and Zika. Herein, we report identifying 129 YFV Class II epitopes in donors vaccinated with the live attenuated YFV vaccine (YFV-17D). A total of 1156 peptides predicted to bind 17 different common HLA-DRB1 allelic variants were tested using IFNγ ELISPOT assays in vitro re-stimulated peripheral blood mononuclear cells from twenty-six vaccinees. Overall, we detected responses against 215 YFV epitopes. We found that the capsid and envelope proteins, as well as the non-structural (NS) proteins NS3 and NS5, were the most targeted proteins by CD4+ T cells from YF-VAX vaccinated donors. In addition, we designed and validated by flow cytometry a CD4+ mega pool (MP) composed of structural and non-structural epitopes in an independent cohort of vaccinated donors. Overall, this study provides a comprehensive prediction and validation of YFV epitopes in a cohort of YF-17D vaccinated individuals. With the design of a CD4 epitope MP, we further provide a useful tool to detect ex vivo responses of YFV-specific CD4 T cells in small sample volumes.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1999-4915/12/11/1300Test; https://doaj.org/toc/1999-4915Test

الوصول الحر: https://doaj.org/article/363087532eec462bab83e8607c89608fTest

المؤلفون: Bjoern Peters, K. M. Y. Fung, J. Greenbaum, Ashu Chawla, Gayani Premawansa, Sunil Premawansa, Jose Mateus, Alessandro Sette, Hannah Voic, Ananda Wijewickrama, V. Pandagrundan, A. Wang, Daniela Weiskopf, Alba Grifoni, Grégory Seumois, R. Tennekon, D. D. De Silva, Rashmi Tippalagama

مصطلحات موضوعية: business.industry, viruses, T cell, virus diseases, Disease, biochemical phenomena, metabolism, and nutrition, Dengue virus, medicine.disease, medicine.disease_cause, Dengue fever, Transcriptome, medicine.anatomical_structure, Immunopathology, Immunology, medicine, Cytotoxic T cell, business, CD8

الوصف: While several lines of evidence suggest a protective role of T cells against disease associated with Dengue virus (DENV) infection, their potential contribution to immunopathology in the acute phase of DENV infection remains controversial, and it has been hypothesized that the more severe form of the disease (dengue hemorrhagic fever, DHF) is associated with altered T cell responses. To address this question, we determined the transcriptomic profiles of DENV-specific CD8+T cells in a cohort of 40 hospitalized DENV donors with either a milder form of the disease (dengue fever, DF) or a more severe disease form (dengue hemorrhagic fever, DHF). We found multiple transcriptomic signatures, one associated with DENV-specific Interferon-gamma responding cells, and two other gene signatures, one specifically associated with the acute phase, and the other with the early convalescent phase. Additionally, we found no differences in quantity and quality of DENV-specific CD8+T cells based on disease severity. Taken together with previous findings that did not detect altered DENV-specific CD4 T cell responses, the current analysis argues against alteration in DENV-specific T cell responses as being a correlate of immunopathology.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0937728c4dc8b833436774c06e14bfb4Test
https://doi.org/10.1101/2021.09.01.21262833Test

المؤلفون: Ricardo da Silva Antunes, Buddy Creech, Natalia Jimenez-Truque, April Frazier, Eric Wang, Stacey Wooden, Hannah Voic, Wayne C. Koff, Esther Dawen Yu, Alba Grifoni, Alessandro Sette, Aaron Sutherland, Sabrina Welsh, Sandra M. Yoder

المصدر: Vaccines, Vol 9, Iss 426, p 426 (2021)
Vaccines
Volume 9
Issue 5

مصطلحات موضوعية: 0301 basic medicine, Quadrivalent Inactivated Influenza Vaccine, Viral protein, Immunology, T cells, Biology, medicine.disease_cause, Virus, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, vaccine, Drug Discovery, medicine, Cytotoxic T cell, biochemistry, Pharmacology (medical), 030212 general & internal medicine, Pharmacology, protein immunodominance, virus diseases, Virology, cytokine polarization, Vaccination, 030104 developmental biology, Infectious Diseases, Medicine, influenza viruses, CD8

الوصف: The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax®, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins. CD4 T cell reactivity was mostly directed to HA/NA proteins in influenza B strains, and NP/M1/M2/NS1/NEP proteins in the case of the Influenza A strains. CD8 responses to both influenza A and B viruses preferentially targeted the more conserved core viral proteins. Following vaccination, both CD4 and CD8 responses against the various influenza antigens were increased in day 15 to day 91 post vaccination period and maintained a Th1 polarized profile. Importantly, no vaccine interference was detected, with the increased responses balanced across all 4 included viral strains for both CD4 and CD8 T cells, and targeting HA and multiple additional viral antigens.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2e9d913001ad701f696ef3b3760188dTest
https://www.mdpi.com/2076-393X/9/5/426Test

المؤلفون: Yohannes Tesfaigzi, Mauricio Rojas, Jonathan K. Alder, Chunbin Zou, Hannah Voic, Xiuying Li, Divay Chandra, Scott H. Randell, Rama K. Mallampalli, Prithu Sundd, Tyrone Ryba, Jun Ho Jang, Toru Nyunoya

المصدر: BMC Genomics, Vol 20, Iss 1, Pp 1-12 (2019)
BMC Genomics

مصطلحات موضوعية: 0106 biological sciences, Senescence, lcsh:QH426-470, Cell Survival, lcsh:Biotechnology, Primary Cell Culture, RNA-Seq, Bronchi, Biology, 01 natural sciences, Cigarette Smoking, Transcriptome, 03 medical and health sciences, lcsh:TP248.13-248.65, Gene expression, Genetics, Humans, Gene, Cellular Senescence, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Sequence Analysis, RNA, NF-kappa B, RNA, Cigarette smoke, Epithelial Cells, NFKB1, 3. Good health, Cell biology, lcsh:Genetics, Primary human bronchial epithelial cells, chemistry, Gene Expression Regulation, Replicative senescence, RNA-seq, Reactive Oxygen Species, 010606 plant biology & botany, Biotechnology, Research Article, Signal Transduction

الوصف: Background Aging is affected by genetic and environmental factors, and cigarette smoking is strongly associated with accumulation of senescent cells. In this study, we wanted to identify genes that may potentially be beneficial for cell survival in response to cigarette smoke and thereby may contribute to development of cellular senescence. Results Primary human bronchial epithelial cells from five healthy donors were cultured, treated with or without 1.5% cigarette smoke extract (CSE) for 24 h or were passaged into replicative senescence. Transcriptome changes were monitored using RNA-seq in CSE and non-CSE exposed cells and those passaged into replicative senescence. We found that, among 1534 genes differentially regulated during senescence and 599 after CSE exposure, 243 were altered in both conditions, representing strong enrichment. Pathways and gene sets overrepresented in both conditions belonged to cellular processes that regulate reactive oxygen species, proteasome degradation, and NF-κB signaling. Conclusions Our results offer insights into gene expression responses during cellular aging and cigarette smoke exposure, and identify potential molecular pathways that are altered by cigarette smoke and may also promote airway epithelial cell senescence. Electronic supplementary material The online version of this article (10.1186/s12864-018-5409-z) contains supplementary material, which is available to authorized users.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee094585b2db1783369b9eb796cbdc31Test
http://link.springer.com/article/10.1186/s12864-018-5409-zTest

المؤلفون: Simon Mallal, Michael A. Angelo, Elizabeth J. Phillips, Hannah Voic, Daniela Weiskopf, Alba Grifoni, Alessandro Sette, Jose Mateus, John Sidney

المصدر: Viruses
Volume 12
Issue 11
Viruses, Vol 12, Iss 1300, p 1300 (2020)

مصطلحات موضوعية: 0301 basic medicine, CD4-Positive T-Lymphocytes, lcsh:QR1-502, T cells, Epitopes, T-Lymphocyte, T-Cell Antigen Receptor Specificity, CD4+ T cells, Biology, Virus, Epitope, lcsh:Microbiology, Article, Dengue fever, Immunophenotyping, 03 medical and health sciences, Viral Proteins, 0302 clinical medicine, Virology, Yellow Fever, medicine, Humans, Alleles, ELISPOT, Yellow fever, Vaccination, Yellow Fever Vaccine, Histocompatibility Antigens Class II, Japanese encephalitis, epitopes, medicine.disease, 030104 developmental biology, Infectious Diseases, Capsid, Yellow fever virus, Peptides, Biomarkers, 030215 immunology, Protein Binding

الوصف: Yellow fever virus (YFV) is a mosquito-borne member of the genus flavivirus, including other important human-pathogenic viruses, such as dengue, Japanese encephalitis, and Zika. Herein, we report identifying 129 YFV Class II epitopes in donors vaccinated with the live attenuated YFV vaccine (YFV-17D). A total of 1156 peptides predicted to bind 17 different common HLA-DRB1 allelic variants were tested using IFN&gamma
ELISPOT assays in vitro re-stimulated peripheral blood mononuclear cells from twenty-six vaccinees. Overall, we detected responses against 215 YFV epitopes. We found that the capsid and envelope proteins, as well as the non-structural (NS) proteins NS3 and NS5, were the most targeted proteins by CD4+ T cells from YF-VAX vaccinated donors. In addition, we designed and validated by flow cytometry a CD4+ mega pool (MP) composed of structural and non-structural epitopes in an independent cohort of vaccinated donors. Overall, this study provides a comprehensive prediction and validation of YFV epitopes in a cohort of YF-17D vaccinated individuals. With the design of a CD4 epitope MP, we further provide a useful tool to detect ex vivo responses of YFV-specific CD4 T cells in small sample volumes.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9184bd8c283c2200caaef7201705d60Test
https://pubmed.ncbi.nlm.nih.gov/33198381Test

المؤلفون: Hannah, Voic, Rory D, de Vries, John, Sidney, Paul, Rubiro, Erin, Moore, Elizabeth, Phillips, Simon, Mallal, Brittany, Schwan, Daniela, Weiskopf, Alessandro, Sette, Alba, Grifoni

المصدر: J Virol

مصطلحات موضوعية: Aged, 80 and over, CD4-Positive T-Lymphocytes, Male, Herpesvirus 3, Human, Immunity, Cellular, Vaccination, Epitopes, T-Lymphocyte, Middle Aged, Antibodies, Viral, Vaccines, Attenuated, Herpes Zoster, Cell Line, Vaccines and Antiviral Agents, Herpes Zoster Vaccine, Humans, Aged

الوصف: Infections with varicella-zoster virus (VZV) are associated with a range of clinical manifestations. Primary infection with VZV causes chicken pox. The virus remains latent in neurons, and it can reactivate later in life, causing herpes zoster (HZ). Two different vaccines have been developed to prevent HZ; one is based on a live attenuated VZV strain (Zostavax), and the other is based on adjuvanted gE recombinant protein (Shingrix). While Zostavax efficacy wanes with age, Shingrix protection retains its efficacy in elderly subjects (individuals 80 years of age and older). In this context, it is of much interest to understand if there is a role for T cell immunity in the differential clinical outcome and if there is a correlate of protection between T cell immunity and Shingrix efficacy. In this study, we characterized the Shingrix-specific ex vivo CD4 T cell responses in the context of natural exposure and HZ vaccination using pools of predicted epitopes. We show that T cell reactivity following natural infection and Zostavax vaccination dominantly targets nonstructural (NS) proteins, while Shingrix vaccination redirects dominant reactivity to target gE. We mapped the gE-specific responses following Shingrix vaccination to 89 different gE epitopes, 34 of which accounted for 80% of the response. Using antigen presentation assays and single HLA molecule-transfected lines, we experimentally determined HLA restrictions for 94 different donor/peptide combinations. Finally, we used our results as a training set to assess strategies to predict restrictions based on measured or predicted HLA binding and the corresponding HLA types of the responding subjects. IMPORTANCE Understanding the T cell profile associated with the protection observed in elderly vaccinees following Shingrix vaccination is relevant to the general definition of correlates of vaccine efficacy. Our study enables these future studies by clarifying the patterns of immunodominance associated with Shingrix vaccination, as opposed to natural infection or Zostavax vaccination. Identification of epitopes recognized by Shingrix-induced CD4 T cells and their associated HLA restrictions enables the generation of tetrameric staining reagents and, more broadly, the capability to characterize the specificity, magnitude, and phenotype of VZV-specific T cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::06fbc818570a588692f0c084edebd279Test
https://pubmed.ncbi.nlm.nih.gov/32999027Test