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B Cells Fit for Germinal Center Activity Predict Response to a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients

E. A. Thompson1, A. H. Karaba1, K. Cascino1, K. Roznik1, T. Chiang1, L. Biavatti1, A. T. Abedon1, J. L. Alejo1, S. L. Klein1, J. N. Blankson1, D. S. Warren1, C. X. Qin1, J. Mitchell1, J. M. Garonzik-Wang2, B. J. Boyarsky1, D. L. Segev1, A. A. Tobian1, W. A. Werbel1, A. L. Cox1, J. R. Bailey1

1Johns Hopkins University, Baltimore, MD, 2University of Wisconsin School of Medicine and Health, Madison, WI

Meeting: 2022 American Transplant Congress

Abstract number: 283

Keywords: Antibodies, B cells, COVID-19, Vaccination

Topic: Basic Science » Basic Science » 04 - B-cell / Antibody /Autoimmunity

Session Information

Session Name: B-cell / Antibody /Autoimmunity

Session Type: Rapid Fire Oral Abstract

Date: Monday, June 6, 2022

Session Time: 3:30pm-5:00pm

 Presentation Time: 4:10pm-4:20pm

Location: Hynes Room 310

*Purpose: While SARS-CoV-2 vaccination has dramatically reduced COVID-19 severity in the general population, fully vaccinated solid organ transplant recipients (SOTRs) demonstrate reduced seroconversion and increased breakthrough infection rates. Furthermore, a third vaccine dose only increases antibody and T cell responses in a proportion of SOTRs. We sought to investigate the underlying mechanisms resulting in varied humoral responses in SOTRs.

*Methods: Within a longitudinal prospective cohort of SOTRs, anti-spike IgG, total and spike-specific B cells were evaluated in 44 SOTR participants before and after a third vaccine dose using high dimensional flow cytometry to assess immunologic and metabolic phenotypes. B cell phenotypes were compared to those of 10 healthy controls who received a standard two-dose mRNA series.

*Results: Notably, even in the absence anti-spike antibody after two doses, spike-specific B cells were detectable in most SOTRs (76%). While 15% of participants were seropositive before the third dose, 72% were seropositive afterward. B cells, however, were differentially skewed towards non-class switched B cells in SOTRs as compared to healthy control B cells. Expansion of spike-specific class-switched B cells in SOTRs following a third vaccine dose correlated with increased class-switched (IgG) antibody titers. Antibody response to a third vaccine dose was associated with expanded populations of germinal center-like (CD10+CD27+) B cells, as well as CD11c+ alternative lineage B cells with specific upregulation of CPT1a, the rate limiting enzyme of fatty acid oxidation and a preferred energy source of germinal center B cells.

*Conclusions: This analysis defines a distinct B cell phenotype in SOTRs who respond to a third SARS-CoV-2 vaccine dose, specifically identifying fatty acid oxidation as pathway that could be targeted to improve vaccine response such as through targeted immunosuppressive modulation.

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To cite this abstract in AMA style:

Thompson EA, Karaba AH, Cascino K, Roznik K, Chiang T, Biavatti L, Abedon AT, Alejo JL, Klein SL, Blankson JN, Warren DS, Qin CX, Mitchell J, Garonzik-Wang JM, Boyarsky BJ, Segev DL, Tobian AA, Werbel WA, Cox AL, Bailey JR. B Cells Fit for Germinal Center Activity Predict Response to a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/b-cells-fit-for-germinal-center-activity-predict-response-to-a-third-dose-of-sars-cov-2-vaccine-in-solid-organ-transplant-recipients/. Accessed May 28, 2025.

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