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

Keywords

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

UN SDGs

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

Access to Document

10.1016/j.xcrm.2023.101017Licence: CC BY-NC-ND

Cite this

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

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 -