Abnormal B Cell Profile Associated with Inadequate Antibody Response to MRNA SARS-COV-2 Vaccine Can Be Overcome with a Third Vaccine Dose in Adolescent Kidney Transplant Recipients. C. Crane
American Journal of Transplantation
; 22(Supplement 3):381, 2022.
Article
in English
| EMBASE | ID: covidwho-2063378
ABSTRACT
Purpose:
mRNA SARS-CoV-2 vaccines are highly efficacious in the general population but have shown a diminished response in immunosuppressed adolescent kidney allograft recipients. We investigated immunological parameters that could be associated with a blunted antibody response. We also analyzed whether a third vaccine dose could improve the antibody response. Method(s) Adolescent kidney transplant recipients who received mRNA SARSCoV- 2 vaccine had SARS-CoV-2 spike protein antibody levels measured 4-8 weeks after their second vaccine dose and again after the third vaccine dose. Immunological labs including lymphocyte subsets, immunoglobulin levels, and vaccine titers and immunosuppressive medication dosing were evaluated prior to vaccination. Patients were compared in groups of vaccine responders vs non-responders via a Mann-Whitney U test. The impact of mycophenolate mofetil dosage on immune parameters was analyzed via a linear regression model. Result(s) 14 of 27 (52%) vaccinated pts had a positive spike antibody level. There was no significant difference in immunoglobulin levels, T-cell populations, or vaccine titers. There was a trend toward negative spike antibodies with higher doses of mycophenolate mofetil, MMF, at 91 mg/m2/day median difference (p=0.06). All four patients receiving azathioprine instead of MMF developed spike antibodies. Non-responders had lower hemoglobin levels (beta=-1.30, p=0.009) and lower platelet count (beta=-56.00, p=0.057). MCV levels were normal in both groups. Non-responders showed a trend toward increased naive B-cell percentage (beta= 12.50, p=0.11) and decreased total memory B-cell percentage (beta=-12.54, p=0.080). Increasing MMF dosage was associated with an increase in naive B-cell percentage (beta=0.016, p=0.0032) decrease in total memory B-cell percentage (beta=-0.016, p=0.0034), and decreased in IgG level (beta=-0.35, p=0.012). Of the 13 patients that did not develop spike antibodies after the second vaccine dose, 9 pts (69%) developed antibodies after the third dose. In total, 23/27 (85%) patients vaccinated developed spiked antibodies. Conclusion(s) Disruption in B-cell population could be due to immunosuppression with MMF. Non-responders showed trends toward high MMF dosage, increased naive B-cell percentage, and decreased total memory B-cell percentage. Increasing MMF dosage was associated with all trends as well as decreased IgG levels. Decreased hemoglobin levels and normal MCV supports that anemia could be due to bone marrow suppression caused by MMF. Altered B-cell populations and MMF therapy are a potential biomarker for reduced efficacy of SARS-CoV-2 vaccine in adolescent kidney allograft recipients. Interestingly, a third vaccine dose can overcome the immunosuppressive effects and improve vaccine efficacy.
adolescent; anemia; antibody response; B lymphocyte; bone marrow suppression; cell population; clinical article; conference abstract; controlled study; drug megadose; drug therapy; female; gene expression; hemoglobin blood level; human; human cell; human tissue; immunoglobulin blood level; immunological parameters; immunosuppressive treatment; kidney allograft; kidney graft; linear regression analysis; lymphocyte subpopulation; male; memory B lymphocyte; nonhuman; platelet count; rank sum test; Severe acute respiratory syndrome coronavirus 2; spike; surgery; T lymphocyte; vaccination; azathioprine; biological marker; endogenous compound; immunoglobulin G; messenger RNA; mycophenolate mofetil; SARS-CoV-2 vaccine; virus spike protein
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Topics:
Vaccines
Language:
English
Journal:
American Journal of Transplantation
Year:
2022
Document Type:
Article
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