RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignancies

The SARS-CoV-2 pandemic still represents a threat for immunosuppressed and hematological malignancy (HM) bearing patients, causing increased morbidity and mortality. Given the low anti-SARSCoV-2 IgG titers post-vaccination, the COVID-19 threat prompted the prophylactic use of engineered anti-SARS-Co...

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Main Authors: Camille Bigenwald, Yacine Haddad, Cassandra Thelemaque, Agathe Carrier, Roxanne Birebent, Pierre Ly, Caroline Flament, Imran Lahmar, Eric de Sousa, Markus Maeurer, Makoto Miyara, Tarek Assi, Cristina Castilla-Llorente, Christophe Willekens, Céline Fayemi, Julien Lazarovici, Aurélien Marabelle, Lisa Derosa, Vincent Ribrag, Laurence Zitvogel
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2022.2163785
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author Camille Bigenwald
Yacine Haddad
Cassandra Thelemaque
Agathe Carrier
Roxanne Birebent
Pierre Ly
Caroline Flament
Imran Lahmar
Eric de Sousa
Markus Maeurer
Makoto Miyara
Tarek Assi
Cristina Castilla-Llorente
Christophe Willekens
Céline Fayemi
Julien Lazarovici
Aurélien Marabelle
Lisa Derosa
Vincent Ribrag
Laurence Zitvogel
author_facet Camille Bigenwald
Yacine Haddad
Cassandra Thelemaque
Agathe Carrier
Roxanne Birebent
Pierre Ly
Caroline Flament
Imran Lahmar
Eric de Sousa
Markus Maeurer
Makoto Miyara
Tarek Assi
Cristina Castilla-Llorente
Christophe Willekens
Céline Fayemi
Julien Lazarovici
Aurélien Marabelle
Lisa Derosa
Vincent Ribrag
Laurence Zitvogel
author_sort Camille Bigenwald
collection DOAJ
description The SARS-CoV-2 pandemic still represents a threat for immunosuppressed and hematological malignancy (HM) bearing patients, causing increased morbidity and mortality. Given the low anti-SARSCoV-2 IgG titers post-vaccination, the COVID-19 threat prompted the prophylactic use of engineered anti-SARS-CoV-2 monoclonal antibodies. In addition, potential clinical significance of T cell responses has been overlooked during the first waves of the pandemic, calling for additional in-depth studies. We reported that the polarity and the repertoire of T cell immune responses govern the susceptibility to SARS-CoV-2 infection in health care workers and solid cancer patients. Here, we longitudinally analyzed humoral and cellular immune responses at each BNT162b2 mRNA vaccine injection in 47 HM patients under therapy. Only one-third of HM, mostly multiple myeloma (MM) bearing patients, could mount S1-RBD-specific IgG responses following BNT162b2 mRNA vaccines. This vaccine elicited a S1-RBD-specific Th1 immune response in about 20% patients, mostly in MM and Hodgkin lymphoma, while exacerbating Th2 responses in the 10% cases that presented this recognition pattern at baseline (mostly rituximab-treated patients). Performing a third booster barely improved the percentage of patients developing an S1-RBD-specific Th1 immunity and failed to seroconvert additional HM patients. Finally, 16 patients were infected with SARS-CoV-2, of whom 6 developed a severe infection. Only S1-RBD-specific Th1 responses were associated with protection against SARS-CoV2 infection, while Th2 responses or anti-S1-RBD IgG titers failed to correlate with protection. These findings herald the paramount relevance of vaccine-induced Th1 immune responses in hematological malignancies.
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spelling doaj-art-e42eb58d71344cc7b958ed1f06d3f9342024-12-27T17:34:39ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2022.2163785RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignanciesCamille Bigenwald0Yacine Haddad1Cassandra Thelemaque2Agathe Carrier3Roxanne Birebent4Pierre Ly5Caroline Flament6Imran Lahmar7Eric de Sousa8Markus Maeurer9Makoto Miyara10Tarek Assi11Cristina Castilla-Llorente12Christophe Willekens13Céline Fayemi14Julien Lazarovici15Aurélien Marabelle16Lisa Derosa17Vincent Ribrag18Laurence Zitvogel19Gustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceImmunoTherapy/ ImmunoSurgery, Champalimaud Centre for the Unknown, Lisboa, PortugalImmunoTherapy/ ImmunoSurgery, Champalimaud Centre for the Unknown, Lisboa, PortugalCentre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Assistance Publique Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceHematology Department, Gustave Roussy Cancer Campus, Villejuif, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceGustave Roussy Cancer Campus (GRCC), Villejuif Cedex, FranceThe SARS-CoV-2 pandemic still represents a threat for immunosuppressed and hematological malignancy (HM) bearing patients, causing increased morbidity and mortality. Given the low anti-SARSCoV-2 IgG titers post-vaccination, the COVID-19 threat prompted the prophylactic use of engineered anti-SARS-CoV-2 monoclonal antibodies. In addition, potential clinical significance of T cell responses has been overlooked during the first waves of the pandemic, calling for additional in-depth studies. We reported that the polarity and the repertoire of T cell immune responses govern the susceptibility to SARS-CoV-2 infection in health care workers and solid cancer patients. Here, we longitudinally analyzed humoral and cellular immune responses at each BNT162b2 mRNA vaccine injection in 47 HM patients under therapy. Only one-third of HM, mostly multiple myeloma (MM) bearing patients, could mount S1-RBD-specific IgG responses following BNT162b2 mRNA vaccines. This vaccine elicited a S1-RBD-specific Th1 immune response in about 20% patients, mostly in MM and Hodgkin lymphoma, while exacerbating Th2 responses in the 10% cases that presented this recognition pattern at baseline (mostly rituximab-treated patients). Performing a third booster barely improved the percentage of patients developing an S1-RBD-specific Th1 immunity and failed to seroconvert additional HM patients. Finally, 16 patients were infected with SARS-CoV-2, of whom 6 developed a severe infection. Only S1-RBD-specific Th1 responses were associated with protection against SARS-CoV2 infection, while Th2 responses or anti-S1-RBD IgG titers failed to correlate with protection. These findings herald the paramount relevance of vaccine-induced Th1 immune responses in hematological malignancies.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2163785COVID-19vaccinationT cell
spellingShingle Camille Bigenwald
Yacine Haddad
Cassandra Thelemaque
Agathe Carrier
Roxanne Birebent
Pierre Ly
Caroline Flament
Imran Lahmar
Eric de Sousa
Markus Maeurer
Makoto Miyara
Tarek Assi
Cristina Castilla-Llorente
Christophe Willekens
Céline Fayemi
Julien Lazarovici
Aurélien Marabelle
Lisa Derosa
Vincent Ribrag
Laurence Zitvogel
RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignancies
OncoImmunology
COVID-19
vaccination
T cell
title RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignancies
title_full RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignancies
title_fullStr RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignancies
title_full_unstemmed RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignancies
title_short RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignancies
title_sort rbd specific th1 responses are associated with vaccine induced protection against sars cov 2 infection in patients with hematological malignancies
topic COVID-19
vaccination
T cell
url https://www.tandfonline.com/doi/10.1080/2162402X.2022.2163785
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