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

Authors:

• 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
• Crawford, Jeremy Chase
• Thomas, Paul G.
• Thursky, Karin A.
• Slavin, Monica A.
• Tam, Constantine S.
• Teh, Benjamin W.
• Kedzierska, Katherine

Details:

Cell Reports Medicine, Volume 4, Issue 4, 2023-04-18

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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.