Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
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
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
View: Text | PDF
Clinical Research and Public Health 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

×

Figure 1

Humoral vaccine responses to third mRNA vaccines after anti-CD20 mAb treatments.

Options: View larger image (or click on image) Download as PowerPoint
Humoral vaccine responses to third mRNA vaccines after anti-CD20 mAb tre...
(A and B) Dot plots of anti–SARS-CoV-2 spike antibody titers (A) and neutralizing antibody titers (B) were evaluated from before the first vaccine (baseline) to 6 months after the third vaccine (V3 + 24 weeks). The median is marked by a horizontal line. The proportion of seropositive participants at each time point is shown above the dot plots and the dotted line indicates the threshold for antibody detection (0.01 μg/mL). Circles represent participants without documented SARS-CoV-2 infections and triangles show those with known prior infection at each time point. Data were evaluated by independent-sample 2-tailed t test. (C) Box-and-whisker plots of the neutralization capacities between controls (pre-V3, n = 18; post-V3, n = 18; 24 weeks post-V3, n = 10) and B cell depletion (pre-V3, n = 67; post-V3, n = 63; 24 weeks post-V3, n = 29) is shown. The median is marked by a horizontal line, with whiskers extending to the farthest point within a maximum of 1.5 × IQR. Independent-sample 2-tailed t tests were performed. (D) Dot plots of anti-spike or anti-RBD antibody concentrations for each variant (Alpha, Beta, Gamma, and Delta) between controls (pre-V3, n = 16; post-V3, n = 15) and B cell–depleted participants (pre-V3, n = 66; post-V3, n = 59). The median is marked by a horizontal line. The proportion of seropositive participants at each time point is shown above the dot plots and the dotted line indicates the threshold for antibody detection (0.01 μg/mL). Independent-sample 2-tailed t tests with Bonferroni’s correction were performed. Ctrl, control participants; BCDT, patients with B cell depletion therapy.