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

2023-03-27

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 L

Trevillyan, Janine

Trubiano, Jason

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

B cells

CD4(+) T cells

CD8(+) T cells

COVID-19 vaccines

SARS-CoV-2

T follicular helper cells

antibody-secreting cells

hematology

memory T cells

tetramer-specific

Journal Article

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10.1016/j.xcrm.2023.101017

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.

link

Cell Reports. Medicine 2023; 4(4)

Cell Reports. Medicine

2666-3791