Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells

Thi H O Nguyen; Louise C Rowntree; Lilith F Allen; Brendon Y Chua; Lukasz Kedzierski; Chhay Lim; Masa Lasica; G Surekha Tennakoon; Natalie R Saunders; Megan Crane; Lynette Chee; John F Seymour; Mary Ann Anderson; Ashley Whitechurch; E Bridie Clemens; Wuji Zhang; So Young Chang; Jennifer R Habel; Xiaoxiao Jia; Hayley A McQuilten; Anastasia A Minervina; Mikhail V Pogorelyy; Priyanka Chaurasia; Jan Petersen; Tejas Menon; Luca Hensen; Jessica A Neil; Francesca L Mordant; Hyon-Xhi Tan; Aira F Cabug; Adam K Wheatley; Stephen J Kent; Kanta Subbarao; Theo Karapanagiotidis; Han Huang; Lynn K Vo; Natalie L Cain; Suellen Nicholson; Florian Krammer; Grace Gibney; Fiona James; Janine M Trevillyan; Jason A Trubiano; Jeni Mitchell; Britt Christensen; Katherine A Bond; Deborah A Williamson; Jamie Rossjohn; Jeremy Chase Crawford; Paul G Thomas; Karin A Thursky; Monica A Slavin; Constantine S Tam; Benjamin W Teh; Katherine Kedzierska

doi:10.1016/j.xcrm.2023.101017

Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells

Thi H O Nguyen, Louise C Rowntree, Lilith F Allen, Brendon Y Chua, Lukasz Kedzierski, Chhay Lim, Masa Lasica, G Surekha Tennakoon, Natalie R Saunders, Megan Crane, Lynette Chee, John F Seymour, Mary Ann Anderson, Ashley Whitechurch, E Bridie Clemens, Wuji Zhang, So Young Chang, Jennifer R Habel, Xiaoxiao Jia, Hayley A McQuiltenAnastasia A Minervina, Mikhail V Pogorelyy, Priyanka Chaurasia, Jan Petersen, Tejas Menon, Luca Hensen, Jessica A Neil, Francesca L Mordant, Hyon-Xhi Tan, Aira F Cabug, Adam K Wheatley, Stephen J Kent, Kanta Subbarao, Theo Karapanagiotidis, Han Huang, Lynn K Vo, Natalie L Cain, Suellen Nicholson, Florian Krammer, Grace Gibney, Fiona James, Janine M Trevillyan, Jason A Trubiano, Jeni Mitchell, Britt Christensen, Katherine A Bond, Deborah A Williamson, Jamie Rossjohn, Jeremy Chase Crawford, Paul G Thomas, Karin A Thursky, Monica A Slavin, Constantine S Tam, Benjamin W Teh^*, Katherine Kedzierska^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	101017
Pages (from-to)	1-22
Number of pages	22
Journal	Cell reports. Medicine
Volume	4
Issue number	4
DOIs	https://doi.org/10.1016/j.xcrm.2023.101017
Publication status	Published - 18 Apr 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Humans
Receptors, Antigen, T-Cell, alpha-beta
COVID-19 vaccines
SARS-CoV-2
BNT162 vaccine
CD8-positive T-lymphocytes
COVID-19
Hematologic neoplasms

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Nguyen, T. H. O., Rowntree, L. C., Allen, L. F., Chua, B. Y., Kedzierski, L., Lim, C., Lasica, M., Tennakoon, G. S., Saunders, N. R., Crane, M., Chee, L., Seymour, J. F., Anderson, M. A., Whitechurch, A., Clemens, E. B., Zhang, W., Chang, S. Y., Habel, J. R., Jia, X., ... Kedzierska, K. (2023). Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells. Cell reports. Medicine, 4(4), 1-22. Article 101017. https://doi.org/10.1016/j.xcrm.2023.101017

@article{b0e3b3ffdd51432aab656bc2e336ee3f,

title = "Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells",

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.",

keywords = "Humans, Receptors, Antigen, T-Cell, alpha-beta, COVID-19 vaccines, SARS-CoV-2, BNT162 vaccine, CD8-positive T-lymphocytes, COVID-19, Hematologic neoplasms",

author = "Nguyen, \{Thi H O\} and Rowntree, \{Louise C\} and Allen, \{Lilith F\} and Chua, \{Brendon Y\} and Lukasz Kedzierski and Chhay Lim and Masa Lasica and Tennakoon, \{G Surekha\} and Saunders, \{Natalie R\} and Megan Crane and Lynette Chee and Seymour, \{John F\} and Anderson, \{Mary Ann\} and Ashley Whitechurch and Clemens, \{E Bridie\} and Wuji Zhang and Chang, \{So Young\} and Habel, \{Jennifer R\} and Xiaoxiao Jia and McQuilten, \{Hayley A\} and Minervina, \{Anastasia A\} and Pogorelyy, \{Mikhail V\} and Priyanka Chaurasia and Jan Petersen and Tejas Menon and Luca Hensen and Neil, \{Jessica A\} and Mordant, \{Francesca L\} and Hyon-Xhi Tan and Cabug, \{Aira F\} and Wheatley, \{Adam K\} and Kent, \{Stephen J\} and Kanta Subbarao and Theo Karapanagiotidis and Han Huang and Vo, \{Lynn K\} and Cain, \{Natalie L\} and Suellen Nicholson and Florian Krammer and Grace Gibney and Fiona James and Trevillyan, \{Janine M\} and Trubiano, \{Jason A\} and Jeni Mitchell and Britt Christensen and Bond, \{Katherine A\} and Williamson, \{Deborah A\} and Jamie Rossjohn and Crawford, \{Jeremy Chase\} and Thomas, \{Paul G\} and Thursky, \{Karin A\} and Slavin, \{Monica A\} and Tam, \{Constantine S\} and Teh, \{Benjamin W\} and Katherine Kedzierska",

note = "Funding: This work was supported by NHMRC L1 to K.K. (\#1173871) and M.A.S. (\#1173791); NHMRC L2 to K.S. (\#1177174); NHMRC EL1 to T.H.O.N. (\#1194036) and A.K.W. (\#1173433); NHMRC EL2 to B.W.T. (\#1195894) and D.A.W. (\#1174555); Research Grants Council of the Hong Kong Special Administrative Region, China (\#T11-712/19-N) to K.K.; the Victorian government (S.J.K. and A.K.W.); a MRFF Award (\#2016062) to K.K., T.H.O.N., L.C.R., A.K.W., S.J.K., J.R., and B.W.T.; a MRFF award (\#2002073) to S.J.K. and A.K.W.; a MRFF Award (\#1202445) to K.K.; a MRFF Award (\#2005544) to K.K., S.J.K., and A.K.W.; NHMRC program grant 1149990 (S.J.K.); NHMRC project grant 1162760 (A.K.W.); NHMRC Synergy grant 2011100 (M.A.S.); and NIH contract CIVC-HRP (HHS-NIH-NIAID-BAA2018) to P.G.T. and K.K. E.B.C. is supported by a NHMRC Peter Doherty Fellowship (\#1091516). W.Z., S.Y.C and J.R.H were supported by a Melbourne Research Scholarship from the University of Melbourne. S.J.K. is supported by NHMRC Senior Principal Research Fellowship (\#1136322). J.R. is supported by an ARC Laureate Fellowship. J.C.C. and P.G.T. are supported by NIH NIAID R01 AI136514-03 and ALSAC at St. Jude. We acknowledge BeiGene for supporting a part of the study. C.S.T. receives research funding from the CLL Global Research Foundation.",

year = "2023",

month = apr,

day = "18",

doi = "10.1016/j.xcrm.2023.101017",

language = "English",

volume = "4",

pages = "1--22",

journal = "Cell reports. Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "4",

}

Nguyen, THO, Rowntree, LC, Allen, LF, Chua, BY, Kedzierski, L, Lim, C, Lasica, M, Tennakoon, GS, Saunders, NR, Crane, M, Chee, L, Seymour, JF, Anderson, MA, Whitechurch, A, Clemens, EB, Zhang, W, Chang, SY, Habel, JR, Jia, X, McQuilten, HA, Minervina, AA, Pogorelyy, MV, Chaurasia, P, Petersen, J, Menon, T, Hensen, L, Neil, JA, Mordant, FL, Tan, H-X, Cabug, AF, Wheatley, AK, Kent, SJ, Subbarao, K, Karapanagiotidis, T, Huang, H, Vo, LK, Cain, NL, Nicholson, S, Krammer, F, Gibney, G, James, F, Trevillyan, JM, Trubiano, JA, Mitchell, J, Christensen, B, Bond, KA, Williamson, DA, Rossjohn, J, Crawford, JC, Thomas, PG, Thursky, KA, Slavin, MA, Tam, CS, Teh, BW & Kedzierska, K 2023, 'Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells', Cell reports. Medicine, vol. 4, no. 4, 101017, pp. 1-22. https://doi.org/10.1016/j.xcrm.2023.101017

TY - JOUR

T1 - Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells

AU - Nguyen, Thi H O

AU - Rowntree, Louise C

AU - Allen, Lilith F

AU - Chua, Brendon Y

AU - Kedzierski, Lukasz

AU - Lim, Chhay

AU - Lasica, Masa

AU - Tennakoon, G Surekha

AU - Saunders, Natalie R

AU - Crane, Megan

AU - Chee, Lynette

AU - Seymour, John F

AU - Anderson, Mary Ann

AU - Whitechurch, Ashley

AU - Clemens, E Bridie

AU - Zhang, Wuji

AU - Chang, So Young

AU - Habel, Jennifer R

AU - Jia, Xiaoxiao

AU - McQuilten, Hayley A

AU - Minervina, Anastasia A

AU - Pogorelyy, Mikhail V

AU - Chaurasia, Priyanka

AU - Petersen, Jan

AU - Menon, Tejas

AU - Hensen, Luca

AU - Neil, Jessica A

AU - Mordant, Francesca L

AU - Tan, Hyon-Xhi

AU - Cabug, Aira F

AU - Wheatley, Adam K

AU - Kent, Stephen J

AU - Subbarao, Kanta

AU - Karapanagiotidis, Theo

AU - Huang, Han

AU - Vo, Lynn K

AU - Cain, Natalie L

AU - Nicholson, Suellen

AU - Krammer, Florian

AU - Gibney, Grace

AU - James, Fiona

AU - Trevillyan, Janine M

AU - Trubiano, Jason A

AU - Mitchell, Jeni

AU - Christensen, Britt

AU - Bond, Katherine A

AU - Williamson, Deborah A

AU - Rossjohn, Jamie

AU - Crawford, Jeremy Chase

AU - Thomas, Paul G

AU - Thursky, Karin A

AU - Slavin, Monica A

AU - Tam, Constantine S

AU - Teh, Benjamin W

AU - Kedzierska, Katherine

N1 - Funding: This work was supported by NHMRC L1 to K.K. (#1173871) and M.A.S. (#1173791); NHMRC L2 to K.S. (#1177174); NHMRC EL1 to T.H.O.N. (#1194036) and A.K.W. (#1173433); NHMRC EL2 to B.W.T. (#1195894) and D.A.W. (#1174555); Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N) to K.K.; the Victorian government (S.J.K. and A.K.W.); a MRFF Award (#2016062) to K.K., T.H.O.N., L.C.R., A.K.W., S.J.K., J.R., and B.W.T.; a MRFF award (#2002073) to S.J.K. and A.K.W.; a MRFF Award (#1202445) to K.K.; a MRFF Award (#2005544) to K.K., S.J.K., and A.K.W.; NHMRC program grant 1149990 (S.J.K.); NHMRC project grant 1162760 (A.K.W.); NHMRC Synergy grant 2011100 (M.A.S.); and NIH contract CIVC-HRP (HHS-NIH-NIAID-BAA2018) to P.G.T. and K.K. E.B.C. is supported by a NHMRC Peter Doherty Fellowship (#1091516). W.Z., S.Y.C and J.R.H were supported by a Melbourne Research Scholarship from the University of Melbourne. S.J.K. is supported by NHMRC Senior Principal Research Fellowship (#1136322). J.R. is supported by an ARC Laureate Fellowship. J.C.C. and P.G.T. are supported by NIH NIAID R01 AI136514-03 and ALSAC at St. Jude. We acknowledge BeiGene for supporting a part of the study. C.S.T. receives research funding from the CLL Global Research Foundation.

PY - 2023/4/18

Y1 - 2023/4/18

N2 - 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.

AB - 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.

KW - Humans

KW - Receptors, Antigen, T-Cell, alpha-beta

KW - COVID-19 vaccines

KW - SARS-CoV-2

KW - BNT162 vaccine

KW - CD8-positive T-lymphocytes

KW - COVID-19

KW - Hematologic neoplasms

UR - https://www.scopus.com/pages/publications/85152405157

U2 - 10.1016/j.xcrm.2023.101017

DO - 10.1016/j.xcrm.2023.101017

M3 - Article

C2 - 37030296

SN - 2666-3791

VL - 4

SP - 1

EP - 22

JO - Cell reports. Medicine

JF - Cell reports. Medicine

IS - 4

M1 - 101017

ER -