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

THO Nguyen; LC Rowntree; LF Allen; BY Chua; L Kedzierski; C Lim; M Lasica; GS Tennakoon; NR Saunders; M Crane; L Chee; JF Seymour; MA Anderson; A Whitechurch; EB Clemens; W Zhang; SY Chang; JR Habel; X Jia; HA McQuilten; AA Minervina; MV Pogorelyy; P Chaurasia; J Petersen; T Menon; L Hensen; JA Neil; FL Mordant; HX Tan; AF Cabug; AK Wheatley; SJ Kent; K Subbarao; T Karapanagiotidis; H Huang; LK Vo; NL Cain; S Nicholson; F Krammer; G Gibney; F James; JM Trevillyan; JA Trubiano; J Mitchell; B Christensen; KA Bond; DA Williamson; J Rossjohn; JC Crawford; PG Thomas; KA Thursky; MA Slavin; CS Tam; BW Teh; K Kedzierska

Journal article

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

THO Nguyen, LC Rowntree, LF Allen, BY Chua, L Kedzierski, C Lim, M Lasica, GS Tennakoon, NR Saunders, M Crane, L Chee, JF Seymour, MA Anderson, A Whitechurch, EB Clemens, W Zhang, SY Chang, JR Habel, X Jia, HA McQuilten Show all

Cell Reports Medicine | Published : 2023

DOI: 10.1016/j.xcrm.2023.101017

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..

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University of Melbourne Researchers

Louise Rowntree Author

Brendon Chua Author

Lukasz Kedzierski Author

Lynette Chui Yen Chee Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

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.