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Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study

BACKGROUND: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. METHODS: In this cohort study, conducted at 5 sites in the Netherlands, we comp...

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Autores principales: Hofsink, Quincy, Haggenburg, Sabine, Lissenberg-Witte, Birgit I., Broers, Annoek E.C., van Doesum, Jaap A., van Binnendijk, Rob S., den Hartog, Gerco, Bhoekhan, Michel S., Haverkate, Nienke J.E., van Meerloo, Johan, Burger, Judith A., Bouhuijs, Joey H., Smits, Gaby P., Wouters, Dorine, van Leeuwen, Ester M.M., Bontkes, Hetty J., Kootstra, Neeltje A., Vogels-Nooijen, Sandra, Rots, Nynke, van Beek, Josine, Heemskerk, Mirjam H.M., Groen, Kazimierz, van Meerten, Tom, Mutsaers, Pim G.N.J., van Gils, Marit J., Goorhuis, Abraham, Rutten, Caroline E., Hazenberg, Mette D., Nijhof, Inger S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10270678/
https://www.ncbi.nlm.nih.gov/pubmed/37337616
http://dx.doi.org/10.1016/j.eclinm.2023.102040
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author Hofsink, Quincy
Haggenburg, Sabine
Lissenberg-Witte, Birgit I.
Broers, Annoek E.C.
van Doesum, Jaap A.
van Binnendijk, Rob S.
den Hartog, Gerco
Bhoekhan, Michel S.
Haverkate, Nienke J.E.
van Meerloo, Johan
Burger, Judith A.
Bouhuijs, Joey H.
Smits, Gaby P.
Wouters, Dorine
van Leeuwen, Ester M.M.
Bontkes, Hetty J.
Kootstra, Neeltje A.
Vogels-Nooijen, Sandra
Rots, Nynke
van Beek, Josine
Heemskerk, Mirjam H.M.
Groen, Kazimierz
van Meerten, Tom
Mutsaers, Pim G.N.J.
van Gils, Marit J.
Goorhuis, Abraham
Rutten, Caroline E.
Hazenberg, Mette D.
Nijhof, Inger S.
author_facet Hofsink, Quincy
Haggenburg, Sabine
Lissenberg-Witte, Birgit I.
Broers, Annoek E.C.
van Doesum, Jaap A.
van Binnendijk, Rob S.
den Hartog, Gerco
Bhoekhan, Michel S.
Haverkate, Nienke J.E.
van Meerloo, Johan
Burger, Judith A.
Bouhuijs, Joey H.
Smits, Gaby P.
Wouters, Dorine
van Leeuwen, Ester M.M.
Bontkes, Hetty J.
Kootstra, Neeltje A.
Vogels-Nooijen, Sandra
Rots, Nynke
van Beek, Josine
Heemskerk, Mirjam H.M.
Groen, Kazimierz
van Meerten, Tom
Mutsaers, Pim G.N.J.
van Gils, Marit J.
Goorhuis, Abraham
Rutten, Caroline E.
Hazenberg, Mette D.
Nijhof, Inger S.
author_sort Hofsink, Quincy
collection PubMed
description BACKGROUND: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. METHODS: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration >10 BAU/mL and a previous SARS-CoV-2 infection as N IgG >14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wild-type (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. FINDINGS: Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. INTERPRETATION: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution. FUNDING: The 10.13039/501100001826Netherlands Organisation for Health Research and Development and 10.13039/100019573Amsterdam UMC.
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spelling pubmed-102706782023-06-16 Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study Hofsink, Quincy Haggenburg, Sabine Lissenberg-Witte, Birgit I. Broers, Annoek E.C. van Doesum, Jaap A. van Binnendijk, Rob S. den Hartog, Gerco Bhoekhan, Michel S. Haverkate, Nienke J.E. van Meerloo, Johan Burger, Judith A. Bouhuijs, Joey H. Smits, Gaby P. Wouters, Dorine van Leeuwen, Ester M.M. Bontkes, Hetty J. Kootstra, Neeltje A. Vogels-Nooijen, Sandra Rots, Nynke van Beek, Josine Heemskerk, Mirjam H.M. Groen, Kazimierz van Meerten, Tom Mutsaers, Pim G.N.J. van Gils, Marit J. Goorhuis, Abraham Rutten, Caroline E. Hazenberg, Mette D. Nijhof, Inger S. eClinicalMedicine Articles BACKGROUND: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. METHODS: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration >10 BAU/mL and a previous SARS-CoV-2 infection as N IgG >14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wild-type (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. FINDINGS: Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. INTERPRETATION: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution. FUNDING: The 10.13039/501100001826Netherlands Organisation for Health Research and Development and 10.13039/100019573Amsterdam UMC. Elsevier 2023-06-15 /pmc/articles/PMC10270678/ /pubmed/37337616 http://dx.doi.org/10.1016/j.eclinm.2023.102040 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Hofsink, Quincy
Haggenburg, Sabine
Lissenberg-Witte, Birgit I.
Broers, Annoek E.C.
van Doesum, Jaap A.
van Binnendijk, Rob S.
den Hartog, Gerco
Bhoekhan, Michel S.
Haverkate, Nienke J.E.
van Meerloo, Johan
Burger, Judith A.
Bouhuijs, Joey H.
Smits, Gaby P.
Wouters, Dorine
van Leeuwen, Ester M.M.
Bontkes, Hetty J.
Kootstra, Neeltje A.
Vogels-Nooijen, Sandra
Rots, Nynke
van Beek, Josine
Heemskerk, Mirjam H.M.
Groen, Kazimierz
van Meerten, Tom
Mutsaers, Pim G.N.J.
van Gils, Marit J.
Goorhuis, Abraham
Rutten, Caroline E.
Hazenberg, Mette D.
Nijhof, Inger S.
Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study
title Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study
title_full Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study
title_fullStr Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study
title_full_unstemmed Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study
title_short Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study
title_sort fourth mrna covid-19 vaccination in immunocompromised patients with haematological malignancies (cobra kai): a cohort study
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10270678/
https://www.ncbi.nlm.nih.gov/pubmed/37337616
http://dx.doi.org/10.1016/j.eclinm.2023.102040
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