Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients
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Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients. / Harberts, Aenne; Schaub, Golda M; Ruether, Darius F; Duengelhoef, Paul M; Brehm, Thomas Theo; Karsten, Hendrik; Fathi, Anahita; Jahnke-Triankowski, Jacqueline; Fischer, Lutz; Addo, Marylyn; Haag, Friedrich; Lütgehetmann, Marc; Lohse, Ansgar W.; Schulze zur Wiesch, Julian; Sterneck, Martina.
In: CLIN GASTROENTEROL H, Vol. 20, No. 11, 11.2022, p. 2558-2566.e5.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients
AU - Harberts, Aenne
AU - Schaub, Golda M
AU - Ruether, Darius F
AU - Duengelhoef, Paul M
AU - Brehm, Thomas Theo
AU - Karsten, Hendrik
AU - Fathi, Anahita
AU - Jahnke-Triankowski, Jacqueline
AU - Fischer, Lutz
AU - Addo, Marylyn
AU - Haag, Friedrich
AU - Lütgehetmann, Marc
AU - Lohse, Ansgar W.
AU - Schulze zur Wiesch, Julian
AU - Sterneck, Martina
N1 - Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.
PY - 2022/11
Y1 - 2022/11
N2 - BACKGROUND & AIMS: Liver transplant recipients (LTRs) show a decreased immune response after 2 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccinations compared with healthy controls (HCs). Here, we investigated the immunogenicity of additional vaccinations.METHODS: In this prospective study, humoral (anti-SARS-CoV-2 receptor-binding domain [anti-S RBD]) and cellular (interferon-gamma release assay) immune responses were determined after mRNA-based SARS-CoV-2 vaccination in 106 LTRs after a third vaccination and in 36 LTRs after a fourth vaccination. Patients with anti-S RBD antibody levels >0.8 arbitrary unit (AU)/mL after vaccination were defined as responders.RESULTS: After 3 vaccinations, 92% (97/106) of LTRs compared with 100% (28/28) of HCs were responders. However, the antibody titer of LTRs was lower compared with HCs (1891.0 vs 21,857.0 AU/mL; P < .001). Between a second and third vaccination (n = 75), the median antibody level increased 67-fold in LTRs. In patients seronegative after 2 vaccinations, a third dose induced seroconversion in 76% (19/25), whereas all HCs were already seropositive after 2 vaccinations. A spike-specific T-cell response was detected in 72% (28/39) after a third vaccination compared with 32% (11/34) after a second vaccination. Independent risk factors for a low antibody response (anti-S RBD <100 AU/mL) were first vaccination within the first year after liver transplant (odds ratio [OR], 8.00; P = .023), estimated glomular filtration rate <45 mL/min (OR, 4.72; P = .006), and low lymphocyte counts (OR, 5.02; P = .008). A fourth vaccination induced a 9-fold increase in the median antibody level and seroconversion in 60% (3/5) of previous non-responders.CONCLUSIONS: A third and fourth SARS-CoV-2 vaccination effectively increases the humoral and cellular immune response of LTRs, but to a lesser extent than in HCs. A fourth vaccination should be generally considered in LTRs.
AB - BACKGROUND & AIMS: Liver transplant recipients (LTRs) show a decreased immune response after 2 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccinations compared with healthy controls (HCs). Here, we investigated the immunogenicity of additional vaccinations.METHODS: In this prospective study, humoral (anti-SARS-CoV-2 receptor-binding domain [anti-S RBD]) and cellular (interferon-gamma release assay) immune responses were determined after mRNA-based SARS-CoV-2 vaccination in 106 LTRs after a third vaccination and in 36 LTRs after a fourth vaccination. Patients with anti-S RBD antibody levels >0.8 arbitrary unit (AU)/mL after vaccination were defined as responders.RESULTS: After 3 vaccinations, 92% (97/106) of LTRs compared with 100% (28/28) of HCs were responders. However, the antibody titer of LTRs was lower compared with HCs (1891.0 vs 21,857.0 AU/mL; P < .001). Between a second and third vaccination (n = 75), the median antibody level increased 67-fold in LTRs. In patients seronegative after 2 vaccinations, a third dose induced seroconversion in 76% (19/25), whereas all HCs were already seropositive after 2 vaccinations. A spike-specific T-cell response was detected in 72% (28/39) after a third vaccination compared with 32% (11/34) after a second vaccination. Independent risk factors for a low antibody response (anti-S RBD <100 AU/mL) were first vaccination within the first year after liver transplant (odds ratio [OR], 8.00; P = .023), estimated glomular filtration rate <45 mL/min (OR, 4.72; P = .006), and low lymphocyte counts (OR, 5.02; P = .008). A fourth vaccination induced a 9-fold increase in the median antibody level and seroconversion in 60% (3/5) of previous non-responders.CONCLUSIONS: A third and fourth SARS-CoV-2 vaccination effectively increases the humoral and cellular immune response of LTRs, but to a lesser extent than in HCs. A fourth vaccination should be generally considered in LTRs.
KW - Mice
KW - Animals
KW - Humans
KW - Liver Transplantation
KW - COVID-19 Vaccines
KW - Prospective Studies
KW - Mice, Inbred BALB C
KW - SARS-CoV-2
KW - COVID-19/prevention & control
KW - Immunity, Cellular
KW - Vaccination
KW - RNA, Messenger
KW - Transplant Recipients
KW - Antibodies, Viral
U2 - 10.1016/j.cgh.2022.06.028
DO - 10.1016/j.cgh.2022.06.028
M3 - SCORING: Journal article
C2 - 35850415
VL - 20
SP - 2558-2566.e5
JO - CLIN GASTROENTEROL H
JF - CLIN GASTROENTEROL H
SN - 1542-3565
IS - 11
ER -