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Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses

Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID‐19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT...

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Autores principales: Beaton, Brendan, Sasson, Sarah C., Rankin, Katherine, Raedemaeker, Juliette, Wong, Alexander, Hastak, Priyanka, Phetsouphanh, Chansavath, Warden, Andrew, Klemm, Vera, Munier, C. Mee Ling, Hoppe, Alexandra Carey, Tea, Fiona, Pillay, Aleha, Stella, Alberto Ospina, Aggarwal, Anupriya, Lavee, Orly, Caterson, Ian D., Turville, Stuart, Kelleher, Anthony D., Brilot, Fabienne, Trotman, Judith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349368/
https://www.ncbi.nlm.nih.gov/pubmed/35607995
http://dx.doi.org/10.1002/ajh.26619
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author Beaton, Brendan
Sasson, Sarah C.
Rankin, Katherine
Raedemaeker, Juliette
Wong, Alexander
Hastak, Priyanka
Phetsouphanh, Chansavath
Warden, Andrew
Klemm, Vera
Munier, C. Mee Ling
Hoppe, Alexandra Carey
Tea, Fiona
Pillay, Aleha
Stella, Alberto Ospina
Aggarwal, Anupriya
Lavee, Orly
Caterson, Ian D.
Turville, Stuart
Kelleher, Anthony D.
Brilot, Fabienne
Trotman, Judith
author_facet Beaton, Brendan
Sasson, Sarah C.
Rankin, Katherine
Raedemaeker, Juliette
Wong, Alexander
Hastak, Priyanka
Phetsouphanh, Chansavath
Warden, Andrew
Klemm, Vera
Munier, C. Mee Ling
Hoppe, Alexandra Carey
Tea, Fiona
Pillay, Aleha
Stella, Alberto Ospina
Aggarwal, Anupriya
Lavee, Orly
Caterson, Ian D.
Turville, Stuart
Kelleher, Anthony D.
Brilot, Fabienne
Trotman, Judith
author_sort Beaton, Brendan
collection PubMed
description Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID‐19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti‐spike immunoglobulin G (IgG) was determined by a high‐sensitivity flow‐cytometric assay, in addition to live‐virus neutralization. Antigen‐specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti‐spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25‐fold lower than TN (245 898) and HC (228 255, p = .0002 for both). Anti‐spike IgG correlated with lymphocyte count (r = .63; p = .002), and time from treatment (r = .56; p = .007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p = .03). In the WM cohort, median anti‐spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p = .0008) and HC (p < .0001). Anti‐spike IgG correlated with neutralization of the delta variant (r = .62, p < .0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p < .0001) for early‐clade and delta. All cohorts had functional T cell responses. Median anti‐spike IgG decreased 4‐fold from second to third dose (p = .004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant.
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spelling pubmed-93493682022-08-04 Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses Beaton, Brendan Sasson, Sarah C. Rankin, Katherine Raedemaeker, Juliette Wong, Alexander Hastak, Priyanka Phetsouphanh, Chansavath Warden, Andrew Klemm, Vera Munier, C. Mee Ling Hoppe, Alexandra Carey Tea, Fiona Pillay, Aleha Stella, Alberto Ospina Aggarwal, Anupriya Lavee, Orly Caterson, Ian D. Turville, Stuart Kelleher, Anthony D. Brilot, Fabienne Trotman, Judith Am J Hematol Research Articles Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID‐19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti‐spike immunoglobulin G (IgG) was determined by a high‐sensitivity flow‐cytometric assay, in addition to live‐virus neutralization. Antigen‐specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti‐spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25‐fold lower than TN (245 898) and HC (228 255, p = .0002 for both). Anti‐spike IgG correlated with lymphocyte count (r = .63; p = .002), and time from treatment (r = .56; p = .007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p = .03). In the WM cohort, median anti‐spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p = .0008) and HC (p < .0001). Anti‐spike IgG correlated with neutralization of the delta variant (r = .62, p < .0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p < .0001) for early‐clade and delta. All cohorts had functional T cell responses. Median anti‐spike IgG decreased 4‐fold from second to third dose (p = .004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant. John Wiley & Sons, Inc. 2022-06-09 /pmc/articles/PMC9349368/ /pubmed/35607995 http://dx.doi.org/10.1002/ajh.26619 Text en © 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Beaton, Brendan
Sasson, Sarah C.
Rankin, Katherine
Raedemaeker, Juliette
Wong, Alexander
Hastak, Priyanka
Phetsouphanh, Chansavath
Warden, Andrew
Klemm, Vera
Munier, C. Mee Ling
Hoppe, Alexandra Carey
Tea, Fiona
Pillay, Aleha
Stella, Alberto Ospina
Aggarwal, Anupriya
Lavee, Orly
Caterson, Ian D.
Turville, Stuart
Kelleher, Anthony D.
Brilot, Fabienne
Trotman, Judith
Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses
title Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses
title_full Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses
title_fullStr Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses
title_full_unstemmed Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses
title_short Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses
title_sort patients with treated indolent lymphomas immunized with bnt162b2 have reduced anti‐spike neutralizing igg to sars‐cov‐2 variants, but preserved antigen‐specific t cell responses
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349368/
https://www.ncbi.nlm.nih.gov/pubmed/35607995
http://dx.doi.org/10.1002/ajh.26619
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