Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
Hiromitsu Asashima, … , Mary M. Tomayko, Erin E. Longbrake
Hiromitsu Asashima, … , Mary M. Tomayko, Erin E. Longbrake
Published August 22, 2023
Citation Information: JCI Insight. 2023;8(16):e168102. https://doi.org/10.1172/jci.insight.168102.
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Clinical Medicine COVID-19

Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination

Abstract

BACKGROUND While B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODS We evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.RESULTS In contrast with control individuals (n = 10), most patients on anti-CD20 therapy (n = 48) did not demonstrate an increase in spike-specific B cells or antibodies after a third dose of vaccine. A third vaccine elicited significantly increased frequencies of spike-specific non-naive T cells. A small subset of B cell–depleted individuals effectively produced spike-specific antibodies, and logistic regression models identified time since last anti-CD20 treatment and lower cumulative exposure to anti-CD20 mAbs as predictors of those having a serologic response. B cell–depleted patients who mounted an antibody response to 3 vaccine doses had persistent humoral immunity 6 months later.CONCLUSION These results demonstrate that serial vaccination strategies can be effective for a subset of B cell–depleted patients.FUNDING The NIH (R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473, U01CA260507, 75N93019C00065, K24 AG042489), NIH HIPC Consortium (U19 AI089992), the National Multiple Sclerosis Society (CA 1061-A-18, RG-1802-30153), the Nancy Taylor Foundation for Chronic Diseases, Erase MS, the Robert Leet and Clara Guthrie Patterson Trust, and the Claude D. Pepper Older Americans Independence Center at Yale (P30 AG21342).

Authors

Hiromitsu Asashima, Dongjoo Kim, Kaicheng Wang, Nikhil Lele, Nicholas C. Buitrago-Pocasangre, Rachel Lutz, Isabella Cruz, Khadir Raddassi, William E. Ruff, Michael K. Racke, JoDell E. Wilson, Tara S. Givens, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Steven H. Kleinstein, Ruth R. Montgomery, Albert C. Shaw, Fangyong Li, Rong Fan, David A. Hafler, Mary M. Tomayko, Erin E. Longbrake

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Figure 2

Spike-specific B cell response to third mRNA vaccines after B cell depletion.

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Spike-specific B cell response to third mRNA vaccines after B cell deple...
(A) Representative flow cytometry of CD19+ B cells and their proportions between controls (n = 10) and B cell–depleted participants (n = 48). Data are represented as mean ± SEM and independent-sample t tests with Bonferroni’s correction were performed. (B) Representative flow cytometry of spike+ B cells and their proportions between controls (n = 10) and B cell depleted (n = 48). Wilcoxon’s signed-rank test (middle) and independent-sample 2-tailed t tests with Bonferroni’s correction were performed. (C and D) Representative flow cytometry of each subset in spike+ B cells and their proportions between pre-V3 and post-V3 in controls (n = 10). UCSM, IgD+CD27+ non–class-switched memory B cells; CSM, IgD–CD27+ class-switched memory B cells; DN, IgD–CD27– double-negative B cells. (E and F) Correlation between the proportion of CD19+ B cells before V3 and the proportion of spike+ B cells (E) or anti–SARS-CoV-2 spike antibody titers (F) after V3 in B cell–depleted participants (n = 47–48). The vertical dotted line represents the value of 0.25% (E). Linear regression is shown with 95% confidence intervals (gray area) and correlation statistics by 2-tailed Spearman’s rank correlation test were performed (F).