TY - JOUR
T1 - Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells
AU - Nguyen, Thi H.O.
AU - Rowntree, Louise C.
AU - Allen, Lilith F.
AU - Chua, Brendon Y.
AU - Kedzierski, Lukasz
AU - Lim, Chhay
AU - Lasica, Masa
AU - Tennakoon, G. Surekha
AU - Saunders, Natalie R.
AU - Crane, Megan
AU - Chee, Lynette
AU - Seymour, John F.
AU - Anderson, Mary Ann
AU - Whitechurch, Ashley
AU - Clemens, E. Bridie
AU - Zhang, Wuji
AU - Chang, So Young
AU - Habel, Jennifer R.
AU - Jia, Xiaoxiao
AU - McQuilten, Hayley A.
AU - Minervina, Anastasia A.
AU - Pogorelyy, Mikhail V.
AU - Chaurasia, Priyanka
AU - Petersen, Jan
AU - Menon, Tejas
AU - Hensen, Luca
AU - Neil, Jessica A.
AU - Mordant, Francesca L.
AU - Tan, Hyon Xhi
AU - Cabug, Aira F.
AU - Wheatley, Adam K.
AU - Kent, Stephen J.
AU - Subbarao, Kanta
AU - Karapanagiotidis, Theo
AU - Huang, Han
AU - Vo, Lynn K.
AU - Cain, Natalie L.
AU - Nicholson, Suellen
AU - Krammer, Florian
AU - Gibney, Grace
AU - James, Fiona
AU - Trevillyan, Janine M.
AU - Trubiano, Jason A.
AU - Mitchell, Jeni
AU - Christensen, Britt
AU - Bond, Katherine A.
AU - Williamson, Deborah A.
AU - Rossjohn, Jamie
AU - Crawford, Jeremy Chase
AU - Thomas, Paul G.
AU - Thursky, Karin A.
AU - Slavin, Monica A.
AU - Tam, Constantine S.
AU - Teh, Benjamin W.
AU - Kedzierska, Katherine
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/4/18
Y1 - 2023/4/18
N2 - 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.
AB - 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.
KW - antibody-secreting cells
KW - B cells
KW - CD4 T cells
KW - CD8 T cells
KW - COVID-19 vaccines
KW - hematology
KW - memory T cells
KW - SARS-CoV-2
KW - T follicular helper cells
KW - tetramer-specific
UR - http://www.scopus.com/inward/record.url?scp=85152405157&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2023.101017
DO - 10.1016/j.xcrm.2023.101017
M3 - Article
C2 - 37030296
AN - SCOPUS:85152405157
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 4
M1 - 101017
ER -