Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients

Background. Severe acute respiratory syndrome coronavirus 2–specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized. Methods. We included 44 (28 kidney, 14 live...

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Autores principales: Mario Fernández-Ruiz, MD, PhD, Patricia Almendro-Vázquez, BSc, Octavio Carretero, BSc, Tamara Ruiz-Merlo, BSN, Rocío Laguna-Goya, MD, PhD, Rafael San Juan, MD, PhD, Francisco López-Medrano, MD, PhD, Estéfani García-Ríos, PhD, Vicente Más, PhD, Miguel Moreno-Batenero, CLS, Carmelo Loinaz, MD, PhD, Amado Andrés, MD, PhD, Pilar Pérez-Romero, PhD, Estela Paz-Artal, MD, PhD, José María Aguado, MD, PhD
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Publicado: Wolters Kluwer 2021
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spelling oai:doaj.org-article:c83d79c5d2694db78f54363cf158fa422021-11-25T07:59:57ZDiscordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients2373-873110.1097/TXD.0000000000001246https://doaj.org/article/c83d79c5d2694db78f54363cf158fa422021-12-01T00:00:00Zhttp://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001246https://doaj.org/toc/2373-8731Background. Severe acute respiratory syndrome coronavirus 2–specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized. Methods. We included 44 (28 kidney, 14 liver, and 2 double organ) recipients who received the full series of the mRNA-1273 vaccine. SARS-CoV-2-CMI was evaluated at baseline, before the second dose, and at 2 wk after completion of vaccination by an ELISpot-based interferon-γ FluoroSpot assay using overlapping peptides covering the S1 domain. SARS-CoV-2 immunoglobulin G seroconversion and serum neutralizing activity against the spike protein were assessed at the same points by commercial ELISA and an angiotensin-converting enzyme-2/spike antibody inhibition method, respectively. Postvaccination SARS-CoV-2-CMI was compared with 28 healthcare workers who received the BNT162b2 vaccine. Results. Positive SARS-CoV-2-CMI increased from 6.8% at baseline to 23.3% after the first mRNA-1273 dose and 59.5% after the completion of vaccination (P < 0.0001). Lower rates were observed for immunoglobulin G seroconversion (2.3%, 18.6%, and 57.1%, respectively) and neutralizing activity (2.3%, 11.6%, and 31.0%). There was a modest correlation between neutralizing titers and the magnitude of SARS-CoV-2-CMI (Spearman’s rho: 0.375; P = 0.015). Fifteen recipients (35.7%) mounted SARS-CoV-2-CMI without detectable neutralizing activity, whereas 3 (7.1%) did the opposite, yielding poor categorical agreement (Kappa statistic: 0.201). Rates of positive SARS-CoV-2-CMI among SOT recipients were significantly decreased compared with nontransplant controls (82.1% and 100.0% after the first dose and completion of vaccination, respectively; P < 0.0001). Kidney transplantation, the use of tacrolimus and prednisone, and the number of immunosuppressive agents were associated with lower cell-mediated responses. Results remained unchanged when 3 recipients with prevaccination SARS-CoV-2-CMI were excluded. Conclusions. Two-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.Mario Fernández-Ruiz, MD, PhDPatricia Almendro-Vázquez, BScOctavio Carretero, BScTamara Ruiz-Merlo, BSNRocío Laguna-Goya, MD, PhDRafael San Juan, MD, PhDFrancisco López-Medrano, MD, PhDEstéfani García-Ríos, PhDVicente Más, PhDMiguel Moreno-Batenero, CLSCarmelo Loinaz, MD, PhDAmado Andrés, MD, PhDPilar Pérez-Romero, PhDEstela Paz-Artal, MD, PhDJosé María Aguado, MD, PhDWolters KluwerarticleSurgeryRD1-811ENTransplantation Direct, Vol 7, Iss 12, p e794 (2021)
institution DOAJ
collection DOAJ
language EN
topic Surgery
RD1-811
spellingShingle Surgery
RD1-811
Mario Fernández-Ruiz, MD, PhD
Patricia Almendro-Vázquez, BSc
Octavio Carretero, BSc
Tamara Ruiz-Merlo, BSN
Rocío Laguna-Goya, MD, PhD
Rafael San Juan, MD, PhD
Francisco López-Medrano, MD, PhD
Estéfani García-Ríos, PhD
Vicente Más, PhD
Miguel Moreno-Batenero, CLS
Carmelo Loinaz, MD, PhD
Amado Andrés, MD, PhD
Pilar Pérez-Romero, PhD
Estela Paz-Artal, MD, PhD
José María Aguado, MD, PhD
Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients
description Background. Severe acute respiratory syndrome coronavirus 2–specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized. Methods. We included 44 (28 kidney, 14 liver, and 2 double organ) recipients who received the full series of the mRNA-1273 vaccine. SARS-CoV-2-CMI was evaluated at baseline, before the second dose, and at 2 wk after completion of vaccination by an ELISpot-based interferon-γ FluoroSpot assay using overlapping peptides covering the S1 domain. SARS-CoV-2 immunoglobulin G seroconversion and serum neutralizing activity against the spike protein were assessed at the same points by commercial ELISA and an angiotensin-converting enzyme-2/spike antibody inhibition method, respectively. Postvaccination SARS-CoV-2-CMI was compared with 28 healthcare workers who received the BNT162b2 vaccine. Results. Positive SARS-CoV-2-CMI increased from 6.8% at baseline to 23.3% after the first mRNA-1273 dose and 59.5% after the completion of vaccination (P < 0.0001). Lower rates were observed for immunoglobulin G seroconversion (2.3%, 18.6%, and 57.1%, respectively) and neutralizing activity (2.3%, 11.6%, and 31.0%). There was a modest correlation between neutralizing titers and the magnitude of SARS-CoV-2-CMI (Spearman’s rho: 0.375; P = 0.015). Fifteen recipients (35.7%) mounted SARS-CoV-2-CMI without detectable neutralizing activity, whereas 3 (7.1%) did the opposite, yielding poor categorical agreement (Kappa statistic: 0.201). Rates of positive SARS-CoV-2-CMI among SOT recipients were significantly decreased compared with nontransplant controls (82.1% and 100.0% after the first dose and completion of vaccination, respectively; P < 0.0001). Kidney transplantation, the use of tacrolimus and prednisone, and the number of immunosuppressive agents were associated with lower cell-mediated responses. Results remained unchanged when 3 recipients with prevaccination SARS-CoV-2-CMI were excluded. Conclusions. Two-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.
format article
author Mario Fernández-Ruiz, MD, PhD
Patricia Almendro-Vázquez, BSc
Octavio Carretero, BSc
Tamara Ruiz-Merlo, BSN
Rocío Laguna-Goya, MD, PhD
Rafael San Juan, MD, PhD
Francisco López-Medrano, MD, PhD
Estéfani García-Ríos, PhD
Vicente Más, PhD
Miguel Moreno-Batenero, CLS
Carmelo Loinaz, MD, PhD
Amado Andrés, MD, PhD
Pilar Pérez-Romero, PhD
Estela Paz-Artal, MD, PhD
José María Aguado, MD, PhD
author_facet Mario Fernández-Ruiz, MD, PhD
Patricia Almendro-Vázquez, BSc
Octavio Carretero, BSc
Tamara Ruiz-Merlo, BSN
Rocío Laguna-Goya, MD, PhD
Rafael San Juan, MD, PhD
Francisco López-Medrano, MD, PhD
Estéfani García-Ríos, PhD
Vicente Más, PhD
Miguel Moreno-Batenero, CLS
Carmelo Loinaz, MD, PhD
Amado Andrés, MD, PhD
Pilar Pérez-Romero, PhD
Estela Paz-Artal, MD, PhD
José María Aguado, MD, PhD
author_sort Mario Fernández-Ruiz, MD, PhD
title Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients
title_short Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients
title_full Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients
title_fullStr Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients
title_full_unstemmed Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients
title_sort discordance between sars-cov-2–specific cell-mediated and antibody responses elicited by mrna-1273 vaccine in kidney and liver transplant recipients
publisher Wolters Kluwer
publishDate 2021
url https://doaj.org/article/c83d79c5d2694db78f54363cf158fa42
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