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

2023; Elsevier BV; Volume: 4; Issue: 4 Linguagem: Inglês

10.1016/j.xcrm.2023.101017

2666-3791

Thi H. O. Nguyen, Louise C. Rowntree, Lilith F. Allen, Brendon Y. Chua, Łukasz Kedzierski, Chhay Lim, Masa Lasica, Gayani S 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 Cain, Suellen Nicholson, Florian Krammer, Grace Gibney, Fiona James, Janine M. Trevillyan, Jason A. Trubiano, Jeni Mitchell, Britt Christensen, Katherine Bond, Deborah A. Williamson, Jamie Rossjohn, Jeremy Chase Crawford, Paul G. Thomas, Karin Thursky, Monica A. Slavin, Constantine S. Tam, Benjamin W. Teh, Katherine Kedzierska,

Immunotherapy and Immune Responses

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.