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 |
| Number of pages | 23 |
| Journal | Cell Reports Medicine |
| Volume | 4 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 18 Apr 2023 |
Keywords
- antibody-secreting cells
- B cells
- CD4 T cells
- CD8 T cells
- COVID-19 vaccines
- hematology
- memory T cells
- SARS-CoV-2
- T follicular helper cells
- tetramer-specific
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In: Cell Reports Medicine, Vol. 4, No. 4, 101017, 18.04.2023.
Research output: Contribution to journal › Article › Research › peer-review
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 Information: We thank B. Cox, M. Fezollari, E. Shilling, and L. Davies for support with the healthy cohort; G. Au-Yeung for support with patients; Melbourne Cytometry Platform for technical assistance; and BEI Resources, NIAID, NIH, for providing the peptide array, SARS-related coronavirus 2 spike (S) glycoprotein, NR-52402. 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. K.K. led the study. K.K. B.W.T. C.S.T. M.A.S. and T.H.O.N. supervised the study. K.K. T.H.O.N. L.C.R. L.F.A. B.Y.C. L.K. L.H. J.A.N. F.L.M. H.-X.T. K.S. T.K. S.N. and D.A.W. designed the experiments. T.H.O.N. L.C.R. L.F.A. B.Y.C. L.K. E.B.C. W.Z. S.Y.C. J.R.H. X.J. L.H. J.A.N. F.L.M. H.-X.T. A.F.C. and T.K. performed and analyzed experiments. H.A.M. T.M. A.A.M. M.V.P. A.F.C. J.C.C. and P.G.T. analyzed data. P.C. J.P. A.K.W. S.J.K. K.S. and J.R. provided crucial reagents. C.L. M.L. G.S.T. N.R.S. M.C. L.C. J.F.S. M.A.A. A.W. K.A.T. M.A.S. C.S.T. and B.W.T. recruited the vaccinated hematology patients. G.G. F.J. J.M.T. J.A.T. J.M. B.C. K.A.B. and D.A.W. recruited the healthy vaccinated cohorts. T.H.O.N. L.C.R. L.F.A. B.W.T. and K.K. wrote the manuscript. All authors reviewed and approved the manuscript. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list F.K. as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. H.A.M. and B.Y.C. are currently consulting for Ena Respiratory. B.W.T. has received research funding from MSD, Seqirus, and Sanofi and is on the advisory board for Moderna, CSL-Behring, and Takeda. Funding Information: The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list F.K. as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. H.A.M. and B.Y.C. are currently consulting for Ena Respiratory. B.W.T. has received research funding from MSD, Seqirus, and Sanofi and is on the advisory board for Moderna, CSL-Behring, and Takeda. Funding Information: We thank B. Cox, M. Fezollari, E. Shilling, and L. Davies for support with the healthy cohort; G. Au-Yeung for support with patients; Melbourne Cytometry Platform for technical assistance; and BEI Resources, NIAID, NIH, for providing the peptide array, SARS-related coronavirus 2 spike (S) glycoprotein, NR-52402. 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 . Publisher Copyright: © 2023 The Author(s)
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 - antibody-secreting cells
KW - B cells
KW - CD4 T cells
KW - CD8 T cells
KW - COVID-19 vaccines
KW - hematology
KW - memory T cells
KW - SARS-CoV-2
KW - T follicular helper cells
KW - tetramer-specific
UR - http://www.scopus.com/inward/record.url?scp=85152405157&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2023.101017
DO - 10.1016/j.xcrm.2023.101017
M3 - Article
C2 - 37030296
AN - SCOPUS:85152405157
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 4
M1 - 101017
ER -