Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients.
liver transplantation
mRNA vaccine
mycophenolate mofetil
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
22
08
2021
revised:
03
02
2022
accepted:
10
02
2022
pubmed:
15
3
2022
medline:
22
6
2022
entrez:
14
3
2022
Statut:
ppublish
Résumé
The long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls. LT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose. One hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively. In COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients. The immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.
Sections du résumé
BACKGROUND & AIMS
The long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls.
METHODS
LT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose.
RESULTS
One hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively.
CONCLUSIONS
In COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients.
LAY SUMMARY
The immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.
Identifiants
pubmed: 35283215
pii: S0168-8278(22)00122-2
doi: 10.1016/j.jhep.2022.02.015
pmc: PMC8908852
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Immunoglobulin G
0
Immunosuppressive Agents
0
Mycophenolic Acid
HU9DX48N0T
BNT162 Vaccine
N38TVC63NU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
152-162Informations de copyright
Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest The authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details.
Références
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Clin Gastroenterol Hepatol. 2022 Jan;20(1):162-172.e9
pubmed: 34509643
Vaccines (Basel). 2021 Jul 04;9(7):
pubmed: 34358154
Vaccines (Basel). 2021 Sep 28;9(10):
pubmed: 34696200
Am J Transplant. 2021 Jul;21(7):2509-2521
pubmed: 33278850
J Hepatol. 2021 Jan;74(1):148-155
pubmed: 32750442
Am J Med. 2002 Oct 1;113(5):428-31
pubmed: 12401539
J Hepatol. 2022 Jan;76(1):237-239
pubmed: 34358567
Hepatol Int. 2020 Dec;14(6):930-943
pubmed: 33099753
Nature. 2021 Feb;590(7847):630-634
pubmed: 33276369
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Diabetes Metab Syndr. 2020 Jul - Aug;14(4):535-545
pubmed: 32408118
Am J Transplant. 2021 Aug;21(8):2785-2794
pubmed: 34092033
J Hepatol. 2021 Aug;75(2):435-438
pubmed: 33892006
Clin Microbiol Rev. 2019 Mar 13;32(2):
pubmed: 30867162
Dig Liver Dis. 2021 Oct;53(10):1232-1234
pubmed: 34393073
Gut. 2020 Oct;69(10):1832-1840
pubmed: 32571972
J Allergy Clin Immunol. 2020 Jul;146(1):110-118
pubmed: 32294485
J Clin Med. 2021 Sep 05;10(17):
pubmed: 34501463
J Viral Hepat. 2021 Jul;28(7):1019-1024
pubmed: 33763966
Am J Transplant. 2021 Dec;21(12):3980-3989
pubmed: 34347934
Am J Transplant. 2020 Nov;20(11):3149-3161
pubmed: 32786152
Nat Med. 2021 Jul;27(7):1205-1211
pubmed: 34002089
Clin Microbiol Infect. 2021 Dec;27(12):1861.e1-1861.e5
pubmed: 34375755
Liver Transpl. 2021 Dec;27(12):1852-1856
pubmed: 34407309
Hepatology. 2021 Aug;74(2):1049-1064
pubmed: 33577086
J Hepatol. 2021 Dec;75(6):1434-1439
pubmed: 34454993
Gastroenterology. 2021 Mar;160(4):1151-1163.e3
pubmed: 33307029
Am J Transplant. 2021 Dec;21(12):3971-3979
pubmed: 34291552
Gut. 2021 Oct;70(10):1914-1924
pubmed: 34281984
J Hepatol. 2021 Apr;74(4):944-951
pubmed: 33563499
JAMA. 2021 Jul 13;326(2):165-176
pubmed: 34255003
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
Dig Liver Dis. 2021 Jun;53(6):677-681
pubmed: 33941488
JAMA. 2021 Jun 1;325(21):2204-2206
pubmed: 33950155