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Boosting corrects a memory B cell defect in SARS-CoV-2 mRNA–vaccinated patients with inflammatory bowel disease
Kathryn A. Pape, … , Alexander Khoruts, Marc K. Jenkins
Kathryn A. Pape, … , Alexander Khoruts, Marc K. Jenkins
Published June 22, 2022
Citation Information: JCI Insight. 2022;7(12):e159618. https://doi.org/10.1172/jci.insight.159618.
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Research Article COVID-19 Immunology

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

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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.

Authors

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

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Figure 1

S1-RBD–specific antibody response after mRNA vaccination.

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S1-RBD–specific antibody response after mRNA vaccination.
(A) Mean log10...
(A) Mean log10 S1-RBD antibody titers (± SEM) for controls (black circles, n = 11–30) and patients with IBD (red circles, n = 3–36) at the indicated times (arrows) after the first, second, and third dose of mRNA vaccine. x axis values are the means of time intervals of 1–3 weeks. For example, a group with 5 samples at 15, 15, 16, 17, and 17 weeks would be assigned an x axis value of 16 weeks. (B–D and H) Log10 S1-RBD antibody titers from individual plasma samples from the indicated groups (B) 3.4, (C) 16, or (H) 27 weeks after the first vaccination. Mean titers are indicated with horizontal bars and a numerical value over each group. Values in each graph were compared with Student’s t test. (E) S1-RBD antibody titers versus neutralizing antibody titers for individual samples from controls (black circles, n = 16) and patients with IBD (red circles, n = 36) 16 weeks after the first vaccination, compared by linear regression. (F and G) Neutralizing antibody titers from individual samples from the indicated group 16 weeks after the first vaccination. Mean titers are indicated with horizontal bars. Values in each graph were compared with Student’s t test. (B–D and F–H) **P < 0.01, ***P < 0.001.

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