Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells
Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivi...
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| Veröffentlicht in: | Cell reports. Medicine 2023-04, Vol.4 (4), p.101017-101017, Article 101017 |
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| creator | Nguyen, Thi H.O. Rowntree, Louise C. Allen, Lilith F. Chua, Brendon Y. Kedzierski, Lukasz Lim, Chhay Lasica, Masa Tennakoon, G. Surekha Saunders, Natalie R. Crane, Megan Chee, Lynette Seymour, John F. Anderson, Mary Ann Whitechurch, Ashley Clemens, E. Bridie Zhang, Wuji Chang, So Young Habel, Jennifer R. Jia, Xiaoxiao McQuilten, Hayley A. Minervina, Anastasia A. Pogorelyy, Mikhail V. Chaurasia, Priyanka Petersen, Jan Menon, Tejas Hensen, Luca Neil, Jessica A. Mordant, Francesca L. Tan, Hyon-Xhi Cabug, Aira F. Wheatley, Adam K. Kent, Stephen J. Subbarao, Kanta Karapanagiotidis, Theo Huang, Han Vo, Lynn K. Cain, Natalie L. Nicholson, Suellen Krammer, Florian Gibney, Grace James, Fiona Trevillyan, Janine M. Trubiano, Jason A. Mitchell, Jeni Christensen, Britt Bond, Katherine A. Williamson, Deborah A. Rossjohn, Jamie Crawford, Jeremy Chase Thomas, Paul G. Thursky, Karin A. Slavin, Monica A. Tam, Constantine S. Teh, Benjamin W. Kedzierska, Katherine |
| description | Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%–75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.
[Display omitted]
•COVID-19 vaccines elicit robust SARS-CoV-2-specific T cells in hematology patients•Prevalent TCRαβ motifs occur within tetramer+ T cells in hematological patients•Conversely, perturbed antibody responses and skewing of Tfh and ASC/Tfh kinetics occur•Breakthrough infection patients have higher antibodies and comparable T cell responses
Nguyen et al. define antibody, B, and T cell responses following COVID-19 vaccination in patients with hematological malignancy that are immunocompromised and vulnerable to severe COVID-19 infection. COVID-19 vaccination induces robust T cell immunity in hematology patients with diseases and treatments impacting B cell immunity irrespective of B cell numbers and antibody responses. |
| doi_str_mv | 10.1016/j.xcrm.2023.101017 |
| format | Article |
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[Display omitted]
•COVID-19 vaccines elicit robust SARS-CoV-2-specific T cells in hematology patients•Prevalent TCRαβ motifs occur within tetramer+ T cells in hematological patients•Conversely, perturbed antibody responses and skewing of Tfh and ASC/Tfh kinetics occur•Breakthrough infection patients have higher antibodies and comparable T cell responses
Nguyen et al. define antibody, B, and T cell responses following COVID-19 vaccination in patients with hematological malignancy that are immunocompromised and vulnerable to severe COVID-19 infection. COVID-19 vaccination induces robust T cell immunity in hematology patients with diseases and treatments impacting B cell immunity irrespective of B cell numbers and antibody responses.</description><identifier>ISSN: 2666-3791</identifier><identifier>EISSN: 2666-3791</identifier><identifier>DOI: 10.1016/j.xcrm.2023.101017</identifier><identifier>PMID: 37030296</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>antibody-secreting cells ; B cells ; BNT162 Vaccine ; CD4+ T cells ; CD8+ T cells ; CD8-Positive T-Lymphocytes ; COVID-19 ; COVID-19 Vaccines ; Hematologic Neoplasms ; hematology ; Humans ; memory T cells ; Receptors, Antigen, T-Cell, alpha-beta ; SARS-CoV-2 ; T follicular helper cells ; tetramer-specific</subject><ispartof>Cell reports. Medicine, 2023-04, Vol.4 (4), p.101017-101017, Article 101017</ispartof><rights>2023 The Author(s)</rights><rights>Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3157-638405f30131165ffd781737cefeeb2bb859a3c2524f8c0de2aee5356d3cb6143</citedby><cites>FETCH-LOGICAL-c3157-638405f30131165ffd781737cefeeb2bb859a3c2524f8c0de2aee5356d3cb6143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37030296$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nguyen, Thi H.O.</creatorcontrib><creatorcontrib>Rowntree, Louise C.</creatorcontrib><creatorcontrib>Allen, Lilith F.</creatorcontrib><creatorcontrib>Chua, Brendon Y.</creatorcontrib><creatorcontrib>Kedzierski, Lukasz</creatorcontrib><creatorcontrib>Lim, Chhay</creatorcontrib><creatorcontrib>Lasica, Masa</creatorcontrib><creatorcontrib>Tennakoon, G. 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Bridie</creatorcontrib><creatorcontrib>Zhang, Wuji</creatorcontrib><creatorcontrib>Chang, So Young</creatorcontrib><creatorcontrib>Habel, Jennifer R.</creatorcontrib><creatorcontrib>Jia, Xiaoxiao</creatorcontrib><creatorcontrib>McQuilten, Hayley A.</creatorcontrib><creatorcontrib>Minervina, Anastasia A.</creatorcontrib><creatorcontrib>Pogorelyy, Mikhail V.</creatorcontrib><creatorcontrib>Chaurasia, Priyanka</creatorcontrib><creatorcontrib>Petersen, Jan</creatorcontrib><creatorcontrib>Menon, Tejas</creatorcontrib><creatorcontrib>Hensen, Luca</creatorcontrib><creatorcontrib>Neil, Jessica A.</creatorcontrib><creatorcontrib>Mordant, Francesca L.</creatorcontrib><creatorcontrib>Tan, Hyon-Xhi</creatorcontrib><creatorcontrib>Cabug, Aira F.</creatorcontrib><creatorcontrib>Wheatley, Adam K.</creatorcontrib><creatorcontrib>Kent, Stephen J.</creatorcontrib><creatorcontrib>Subbarao, Kanta</creatorcontrib><creatorcontrib>Karapanagiotidis, Theo</creatorcontrib><creatorcontrib>Huang, Han</creatorcontrib><creatorcontrib>Vo, Lynn K.</creatorcontrib><creatorcontrib>Cain, Natalie L.</creatorcontrib><creatorcontrib>Nicholson, Suellen</creatorcontrib><creatorcontrib>Krammer, Florian</creatorcontrib><creatorcontrib>Gibney, Grace</creatorcontrib><creatorcontrib>James, Fiona</creatorcontrib><creatorcontrib>Trevillyan, Janine M.</creatorcontrib><creatorcontrib>Trubiano, Jason A.</creatorcontrib><creatorcontrib>Mitchell, Jeni</creatorcontrib><creatorcontrib>Christensen, Britt</creatorcontrib><creatorcontrib>Bond, Katherine A.</creatorcontrib><creatorcontrib>Williamson, Deborah A.</creatorcontrib><creatorcontrib>Rossjohn, Jamie</creatorcontrib><creatorcontrib>Crawford, Jeremy Chase</creatorcontrib><creatorcontrib>Thomas, Paul G.</creatorcontrib><creatorcontrib>Thursky, Karin A.</creatorcontrib><creatorcontrib>Slavin, Monica A.</creatorcontrib><creatorcontrib>Tam, Constantine S.</creatorcontrib><creatorcontrib>Teh, Benjamin W.</creatorcontrib><creatorcontrib>Kedzierska, Katherine</creatorcontrib><title>Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells</title><title>Cell reports. Medicine</title><addtitle>Cell Rep Med</addtitle><description>Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%–75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.
[Display omitted]
•COVID-19 vaccines elicit robust SARS-CoV-2-specific T cells in hematology patients•Prevalent TCRαβ motifs occur within tetramer+ T cells in hematological patients•Conversely, perturbed antibody responses and skewing of Tfh and ASC/Tfh kinetics occur•Breakthrough infection patients have higher antibodies and comparable T cell responses
Nguyen et al. define antibody, B, and T cell responses following COVID-19 vaccination in patients with hematological malignancy that are immunocompromised and vulnerable to severe COVID-19 infection. COVID-19 vaccination induces robust T cell immunity in hematology patients with diseases and treatments impacting B cell immunity irrespective of B cell numbers and antibody responses.</description><subject>antibody-secreting cells</subject><subject>B cells</subject><subject>BNT162 Vaccine</subject><subject>CD4+ T cells</subject><subject>CD8+ T cells</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>COVID-19</subject><subject>COVID-19 Vaccines</subject><subject>Hematologic Neoplasms</subject><subject>hematology</subject><subject>Humans</subject><subject>memory T cells</subject><subject>Receptors, Antigen, T-Cell, alpha-beta</subject><subject>SARS-CoV-2</subject><subject>T follicular helper cells</subject><subject>tetramer-specific</subject><issn>2666-3791</issn><issn>2666-3791</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UUtuFDEQtRCIRCEXYIG8ZNODP9N2t8QmdPhEihRpMmRrud3VE4_admN7EnIOLsAV4AgcIGeiWzMgVqyqVHrvVdV7CL2kZEEJFW-2i68mugUjjM8DQuUTdMyEEAWXNX36T3-ETlPaEkJYSWnFyXN0xCXhhNXiGH1bhXaXMr4-W10XTbgpGF7_-m5gGHCENAafIOF7m2-xCc4Fj9fN6vHH40_sQrZ9wjnc69jh5urm4rygNb7Txlg_cazHo84WfD7wb8HpHIawsUYP2OnBbrz25gFbN2qTrd_gd3henF6gZ70eEpwe6gn6_OH9uvlUXF59vGjOLgvDaSkLwaslKXtOKKdUlH3fyYpKLg30AC1r26qsNTesZMu-MqQDpgFKXoqOm1bQJT9Br_e6YwxfdpCycjbNF2gPYZcUk3UlKa8pm6BsDzUxpBShV2O0TscHRYma81BbNeeh5jzUPo-J9Oqgv2sddH8pf9yfAG_3AJi-vLMQVTKTYwY6G8Fk1QX7P_3f2N6eFg</recordid><startdate>20230418</startdate><enddate>20230418</enddate><creator>Nguyen, Thi H.O.</creator><creator>Rowntree, Louise C.</creator><creator>Allen, Lilith F.</creator><creator>Chua, Brendon Y.</creator><creator>Kedzierski, Lukasz</creator><creator>Lim, Chhay</creator><creator>Lasica, Masa</creator><creator>Tennakoon, G. 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Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nguyen, Thi H.O.</au><au>Rowntree, Louise C.</au><au>Allen, Lilith F.</au><au>Chua, Brendon Y.</au><au>Kedzierski, Lukasz</au><au>Lim, Chhay</au><au>Lasica, Masa</au><au>Tennakoon, G. Surekha</au><au>Saunders, Natalie R.</au><au>Crane, Megan</au><au>Chee, Lynette</au><au>Seymour, John F.</au><au>Anderson, Mary Ann</au><au>Whitechurch, Ashley</au><au>Clemens, E. Bridie</au><au>Zhang, Wuji</au><au>Chang, So Young</au><au>Habel, Jennifer R.</au><au>Jia, Xiaoxiao</au><au>McQuilten, Hayley A.</au><au>Minervina, Anastasia A.</au><au>Pogorelyy, Mikhail V.</au><au>Chaurasia, Priyanka</au><au>Petersen, Jan</au><au>Menon, Tejas</au><au>Hensen, Luca</au><au>Neil, Jessica A.</au><au>Mordant, Francesca L.</au><au>Tan, Hyon-Xhi</au><au>Cabug, Aira F.</au><au>Wheatley, Adam K.</au><au>Kent, Stephen J.</au><au>Subbarao, Kanta</au><au>Karapanagiotidis, Theo</au><au>Huang, Han</au><au>Vo, Lynn K.</au><au>Cain, Natalie L.</au><au>Nicholson, Suellen</au><au>Krammer, Florian</au><au>Gibney, Grace</au><au>James, Fiona</au><au>Trevillyan, Janine M.</au><au>Trubiano, Jason A.</au><au>Mitchell, Jeni</au><au>Christensen, Britt</au><au>Bond, Katherine A.</au><au>Williamson, Deborah A.</au><au>Rossjohn, Jamie</au><au>Crawford, Jeremy Chase</au><au>Thomas, Paul G.</au><au>Thursky, Karin A.</au><au>Slavin, Monica A.</au><au>Tam, Constantine S.</au><au>Teh, Benjamin W.</au><au>Kedzierska, Katherine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells</atitle><jtitle>Cell reports. Medicine</jtitle><addtitle>Cell Rep Med</addtitle><date>2023-04-18</date><risdate>2023</risdate><volume>4</volume><issue>4</issue><spage>101017</spage><epage>101017</epage><pages>101017-101017</pages><artnum>101017</artnum><issn>2666-3791</issn><eissn>2666-3791</eissn><abstract>Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%–75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.
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•COVID-19 vaccines elicit robust SARS-CoV-2-specific T cells in hematology patients•Prevalent TCRαβ motifs occur within tetramer+ T cells in hematological patients•Conversely, perturbed antibody responses and skewing of Tfh and ASC/Tfh kinetics occur•Breakthrough infection patients have higher antibodies and comparable T cell responses
Nguyen et al. define antibody, B, and T cell responses following COVID-19 vaccination in patients with hematological malignancy that are immunocompromised and vulnerable to severe COVID-19 infection. COVID-19 vaccination induces robust T cell immunity in hematology patients with diseases and treatments impacting B cell immunity irrespective of B cell numbers and antibody responses.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37030296</pmid><doi>10.1016/j.xcrm.2023.101017</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2666-3791 |
| ispartof | Cell reports. Medicine, 2023-04, Vol.4 (4), p.101017-101017, Article 101017 |
| issn | 2666-3791 2666-3791 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2798713912 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | antibody-secreting cells B cells BNT162 Vaccine CD4+ T cells CD8+ T cells CD8-Positive T-Lymphocytes COVID-19 COVID-19 Vaccines Hematologic Neoplasms hematology Humans memory T cells Receptors, Antigen, T-Cell, alpha-beta SARS-CoV-2 T follicular helper cells tetramer-specific |
| title | Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T00%3A21%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Robust%20SARS-CoV-2%20T%C2%A0cell%20responses%20with%20common%20TCR%CE%B1%CE%B2%20motifs%20toward%20COVID-19%20vaccines%20in%20patients%20with%20hematological%20malignancy%20impacting%20B%20cells&rft.jtitle=Cell%20reports.%20Medicine&rft.au=Nguyen,%20Thi%20H.O.&rft.date=2023-04-18&rft.volume=4&rft.issue=4&rft.spage=101017&rft.epage=101017&rft.pages=101017-101017&rft.artnum=101017&rft.issn=2666-3791&rft.eissn=2666-3791&rft_id=info:doi/10.1016/j.xcrm.2023.101017&rft_dat=%3Cproquest_cross%3E2798713912%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2798713912&rft_id=info:pmid/37030296&rft_els_id=S2666379123001271&rfr_iscdi=true |