B Cells Fit for Germinal Center Activity Predict Response to a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients
American Journal of Transplantation
; 22(Supplement 3):457, 2022.
Article
in English
| EMBASE | ID: covidwho-2063392
ABSTRACT
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. Method(s) 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. Result(s) Notably, even in the absence anti-spike antibody after two doses, spikespecific 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 classswitched (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. Conclusion(s) 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. (Figure Presented).
adult; antibody response; B lymphocyte; clinical article; cohort analysis; conference abstract; controlled study; drug therapy; energy resource; fatty acid oxidation; female; flow cytometry; germinal center; graft recipient; human; human cell; humoral immunity; male; metabolic phenotype; prospective study; spike; upregulation; carnitine palmitoyltransferase I; endogenous compound; immunoglobulin G; immunoglobulin G antibody; messenger RNA; SARS-CoV-2 vaccine
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Prognostic study
Topics:
Vaccines
Language:
English
Journal:
American Journal of Transplantation
Year:
2022
Document Type:
Article
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