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

Nguyen, Thi H.O., Rowntree, Louise C., Allen, Lilith F., Chua, Brendon Y., Kedzierski, Lukasz, Lim, Chhay, Lasica, Masa, Tennakoon, G. Surekha, Saunders, Natalie R., Crane, Megan, Chee, Lynette, Seymour, John F., Anderson, Mary Ann, Whitechurch, Ashley, Clemens, E. Bridie, Zhang, Wuji, Chang, So Young, Habel, Jennifer R., Jia, Xiaoxiao, McQuilten, Hayley A., Minervina, Anastasia A., Pogorelyy, Mikhail V., Chaurasia, Priyanka, Petersen, Jan, Menon, Tejas, Hensen, Luca, Neil, Jessica A., Mordant, Francesca L., Tan, Hyon-Xhi, Cabug, Aira F., Wheatley, Adam K., Kent, Stephen J., Subbarao, Kanta, Karapanagiotidis, Theo, Huang, Han, Vo, Lynn K., Cain, Natalie L., Nicholson, Suellen, Krammer, Florian, Gibney, Grace, James, Fiona, Trevillyan, Janine M., Trubiano, Jason A., Mitchell, Jeni, Christensen, Britt, Bond, Katherine A., Williamson, Deborah A., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Crawford, Jeremy Chase, Thomas, Paul G., Thursky, Karin A., Slavin, Monica A., Tam, Constantine S., Teh, Benjamin W. and Kedzierska, Katherine 2023. Robust SARS-CoV-2 T cell responses with common TCR?? motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells. Cell Reports Medicine 4 (4) , 101017. 10.1016/j.xcrm.2023.101017

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Cell Press
ISSN:	2666-3791
Date of First Compliant Deposit:	15 May 2023
Date of Acceptance:	22 March 2023
Last Modified:	17 May 2023 13:37
URI:	https://orca.cardiff.ac.uk/id/eprint/159523

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