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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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 languageEnglish (US)
Article numbere159618
JournalJCI Insight
Issue number12
StatePublished - 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.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


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