Boosting corrects a memory B cell defect in SARS-CoV-2 mRNA-vaccinated patients with inflammatory bowel disease

Kathryn A. Pape; Thamotharampillai Dileepan; Will Matchett; Charles Ellwood; Samuel Stresemann; Amanda J Kabage; Daria Kozysa; Clayton J Evert; Michael Matson; Sharon Lopez; Peter Krueger; Carolyn T Graiziger; Byron P. Vaughn; Eugenia Shmidt; Joshua Rhein; Timothy W. Schacker; Tyler D Bold; Ryan A. Langlois; Alexander Khoruts; Marc Jenkins

doi:10.1172/jci.insight.159618

Boosting corrects a memory B cell defect in SARS-CoV-2 mRNA-vaccinated patients with inflammatory bowel disease

Kathryn A. Pape, Thamotharampillai Dileepan, Will Matchett, Charles Ellwood, Samuel Stresemann, Amanda J Kabage, Daria Kozysa, Clayton J Evert, Michael Matson, Sharon Lopez, Peter Krueger, Carolyn T Graiziger, Byron P. Vaughn, Eugenia Shmidt, Joshua Rhein, Timothy W. Schacker, Tyler D Bold, Ryan A. Langlois, Alexander Khoruts, Marc Jenkins

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4 Scopus citations

Abstract

Immunosuppressed patients with inflammatory bowel disease (IBD) generate lower amounts of SARS-CoV-2 spike antibodies after mRNA vaccination than healthy controls. We assessed SARS-CoV-2 spike S1 receptor binding domain-specific (S1-RBD-specific) B lymphocytes to identify the underlying cellular defects. Patients with IBD produced fewer anti-S1-RBD antibody-secreting B cells than controls after the first mRNA vaccination and lower amounts of total and neutralizing antibodies after the second. S1-RBD-specific memory B cells were generated to the same degree in IBD and control groups and were numerically stable for 5 months. However, the memory B cells in patients with IBD had a lower S1-RBD-binding capacity than those in controls, which is indicative of a defect in antibody affinity maturation. Administration of a third shot to patients with IBD elevated serum antibodies and generated memory B cells with a normal antigen-binding capacity. These results show that patients with IBD have defects in the formation of antibody-secreting B cells and affinity-matured memory B cells that are corrected by a third vaccination.

Original language	English (US)
Article number	e159618
Journal	JCI Insight
Volume	7
Issue number	12
DOIs	https://doi.org/10.1172/jci.insight.159618
State	Published - Jun 22 2022

Bibliographical note

Funding Information:
The authors acknowledge the contributions of the University of Minnesota Clinical Translational Science Institute, including Carrie McKenzie, Francoise Mercadier-Crevel, and Sydney Viel, in the start-up of this study. This work was supported by a special grant from the Office of the Dean of the University of Minnesota Medical School. Partial funding for the clinical efforts was provided by the nonprofit organization Achieving Cures Together. Flow cytometry was performed in the University of Minnesota Flow Cytometry Resource.

Publisher Copyright:
© 2022, Pape et al.

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Pape, K. A., Dileepan, T., Matchett, W., Ellwood, C., Stresemann, S., Kabage, A. J., Kozysa, D., Evert, C. J., Matson, M., Lopez, S., Krueger, P., Graiziger, C. T., Vaughn, B. P., Shmidt, E., Rhein, J., Schacker, T. W., Bold, T. D., Langlois, R. A., Khoruts, A., & Jenkins, M. (2022). Boosting corrects a memory B cell defect in SARS-CoV-2 mRNA-vaccinated patients with inflammatory bowel disease. JCI Insight, 7(12), Article e159618. https://doi.org/10.1172/jci.insight.159618

Pape, KA , Dileepan, T, Matchett, W, Ellwood, C, Stresemann, S, Kabage, AJ, Kozysa, D, Evert, CJ, Matson, M , Lopez, S, Krueger, P, Graiziger, CT, Vaughn, BP , Shmidt, E , Rhein, J , Schacker, TW , Bold, TD , Langlois, RA , Khoruts, A & Jenkins, M 2022, 'Boosting corrects a memory B cell defect in SARS-CoV-2 mRNA-vaccinated patients with inflammatory bowel disease', JCI Insight, vol. 7, no. 12, e159618. https://doi.org/10.1172/jci.insight.159618

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title = "Boosting corrects a memory B cell defect in SARS-CoV-2 mRNA-vaccinated patients with inflammatory bowel disease",

abstract = "Immunosuppressed patients with inflammatory bowel disease (IBD) generate lower amounts of SARS-CoV-2 spike antibodies after mRNA vaccination than healthy controls. We assessed SARS-CoV-2 spike S1 receptor binding domain-specific (S1-RBD-specific) B lymphocytes to identify the underlying cellular defects. Patients with IBD produced fewer anti-S1-RBD antibody-secreting B cells than controls after the first mRNA vaccination and lower amounts of total and neutralizing antibodies after the second. S1-RBD-specific memory B cells were generated to the same degree in IBD and control groups and were numerically stable for 5 months. However, the memory B cells in patients with IBD had a lower S1-RBD-binding capacity than those in controls, which is indicative of a defect in antibody affinity maturation. Administration of a third shot to patients with IBD elevated serum antibodies and generated memory B cells with a normal antigen-binding capacity. These results show that patients with IBD have defects in the formation of antibody-secreting B cells and affinity-matured memory B cells that are corrected by a third vaccination.",

author = "Pape, {Kathryn A.} and Thamotharampillai Dileepan and Will Matchett and Charles Ellwood and Samuel Stresemann and Kabage, {Amanda J} and Daria Kozysa and Evert, {Clayton J} and Michael Matson and Sharon Lopez and Peter Krueger and Graiziger, {Carolyn T} and Vaughn, {Byron P.} and Eugenia Shmidt and Joshua Rhein and Schacker, {Timothy W.} and Bold, {Tyler D} and Langlois, {Ryan A.} and Alexander Khoruts and Marc Jenkins",

note = "Funding Information: The authors acknowledge the contributions of the University of Minnesota Clinical Translational Science Institute, including Carrie McKenzie, Francoise Mercadier-Crevel, and Sydney Viel, in the start-up of this study. This work was supported by a special grant from the Office of the Dean of the University of Minnesota Medical School. Partial funding for the clinical efforts was provided by the nonprofit organization Achieving Cures Together. Flow cytometry was performed in the University of Minnesota Flow Cytometry Resource. Publisher Copyright: {\textcopyright} 2022, Pape et al.",

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AU - Pape, Kathryn A.

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AU - Matchett, Will

AU - Ellwood, Charles

AU - Stresemann, Samuel

AU - Kabage, Amanda J

AU - Kozysa, Daria

AU - Evert, Clayton J

AU - Matson, Michael

AU - Lopez, Sharon

AU - Krueger, Peter

AU - Graiziger, Carolyn T

AU - Vaughn, Byron P.

AU - Shmidt, Eugenia

AU - Rhein, Joshua

AU - Schacker, Timothy W.

AU - Bold, Tyler D

AU - Langlois, Ryan A.

AU - Khoruts, Alexander

AU - Jenkins, Marc

N1 - Funding Information: The authors acknowledge the contributions of the University of Minnesota Clinical Translational Science Institute, including Carrie McKenzie, Francoise Mercadier-Crevel, and Sydney Viel, in the start-up of this study. This work was supported by a special grant from the Office of the Dean of the University of Minnesota Medical School. Partial funding for the clinical efforts was provided by the nonprofit organization Achieving Cures Together. Flow cytometry was performed in the University of Minnesota Flow Cytometry Resource. Publisher Copyright: © 2022, Pape et al.

PY - 2022/6/22

Y1 - 2022/6/22

N2 - Immunosuppressed patients with inflammatory bowel disease (IBD) generate lower amounts of SARS-CoV-2 spike antibodies after mRNA vaccination than healthy controls. We assessed SARS-CoV-2 spike S1 receptor binding domain-specific (S1-RBD-specific) B lymphocytes to identify the underlying cellular defects. Patients with IBD produced fewer anti-S1-RBD antibody-secreting B cells than controls after the first mRNA vaccination and lower amounts of total and neutralizing antibodies after the second. S1-RBD-specific memory B cells were generated to the same degree in IBD and control groups and were numerically stable for 5 months. However, the memory B cells in patients with IBD had a lower S1-RBD-binding capacity than those in controls, which is indicative of a defect in antibody affinity maturation. Administration of a third shot to patients with IBD elevated serum antibodies and generated memory B cells with a normal antigen-binding capacity. These results show that patients with IBD have defects in the formation of antibody-secreting B cells and affinity-matured memory B cells that are corrected by a third vaccination.

AB - Immunosuppressed patients with inflammatory bowel disease (IBD) generate lower amounts of SARS-CoV-2 spike antibodies after mRNA vaccination than healthy controls. We assessed SARS-CoV-2 spike S1 receptor binding domain-specific (S1-RBD-specific) B lymphocytes to identify the underlying cellular defects. Patients with IBD produced fewer anti-S1-RBD antibody-secreting B cells than controls after the first mRNA vaccination and lower amounts of total and neutralizing antibodies after the second. S1-RBD-specific memory B cells were generated to the same degree in IBD and control groups and were numerically stable for 5 months. However, the memory B cells in patients with IBD had a lower S1-RBD-binding capacity than those in controls, which is indicative of a defect in antibody affinity maturation. Administration of a third shot to patients with IBD elevated serum antibodies and generated memory B cells with a normal antigen-binding capacity. These results show that patients with IBD have defects in the formation of antibody-secreting B cells and affinity-matured memory B cells that are corrected by a third vaccination.

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Boosting corrects a memory B cell defect in SARS-CoV-2 mRNA-vaccinated patients with inflammatory bowel disease

Abstract

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