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

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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 languageEnglish
Article number101017
JournalCell Reports Medicine
Volume4
Issue number4
DOIs
Publication statusPublished - 18 Apr 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

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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