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.

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@article{41e48e89d8204d908d6c06ed3acc59cd,
title = "Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients",
abstract = "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.",
keywords = "Mice, Animals, Humans, Liver Transplantation, COVID-19 Vaccines, Prospective Studies, Mice, Inbred BALB C, SARS-CoV-2, COVID-19/prevention & control, Immunity, Cellular, Vaccination, RNA, Messenger, Transplant Recipients, Antibodies, Viral",
author = "Aenne Harberts and Schaub, {Golda M} and Ruether, {Darius F} and Duengelhoef, {Paul M} and Brehm, {Thomas Theo} and Hendrik Karsten and Anahita Fathi and Jacqueline Jahnke-Triankowski and Lutz Fischer and Marylyn Addo and Friedrich Haag and Marc L{\"u}tgehetmann and Lohse, {Ansgar W.} and {Schulze zur Wiesch}, Julian and Martina Sterneck",
note = "Copyright {\textcopyright} 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.",
year = "2022",
month = nov,
doi = "10.1016/j.cgh.2022.06.028",
language = "English",
volume = "20",
pages = "2558--2566.e5",
journal = "CLIN GASTROENTEROL H",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "11",

}

RIS

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 -