scholarly journals Antibody response to a fourth mRNA Covid-19 vaccine boost in weak responder kidney transplant recipients

2021 ◽  
Author(s):  
Sophie Caillard ◽  
Olivier Thaunat ◽  
Ilies Benotmane ◽  
christophe masset ◽  
Gilles Blancho
Keyword(s):  
Antibody Response ◽  
Kidney Transplant ◽  
Organ Transplant ◽  
Vaccine Dose ◽  
Immunosuppressive Drugs ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Fourth Dose ◽  
Us Fda

The US FDA has recently authorized immunocompromised people to receive a third dose of mRNA Covid-19 vaccine following the two-doses regimen to further boost protection. Unfortunately, a non-negligible proportion of people treated with immunosuppressive drugs either do not respond or show only a weak response after a third boost and should, therefore, still be considered at risk of severe Covid-19. As of June 2021, we were granted the opportunity to offer a fourth vaccine dose to French solid organ transplant recipients who still showed a weak antibody response after the third dose. In this multicenter study, we demonstrate that that the protection conferred by a fourth dose is adequate for the majority of kidney transplant recipients

scholarly journals Humoral Immune Response to SARS-CoV-2 Vaccination after a Booster Vaccine Dose in Two Kidney Transplant Recipients with Fabry Disease and Variable Secondary Immunosuppressive Regimens

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1412
Author(s):  
Lavinia Bernea ◽  
Oana R. Ailioaie ◽  
Nadine Benhamouda ◽  
Eric Tartour ◽  
Dominique P. Germain
Keyword(s):  
Fabry Disease ◽  
Organ Transplant ◽  
Vaccine Dose ◽  
Original Strain ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Success Rates ◽  
Kidney Transplant Recipients ◽  
Protection Measures ◽  
Renal Graft

The urgent need to fight the COVID-19 pandemic has accelerated the development of vaccines against SARS-CoV-2 and approval processes. Initial analysis of two-dose regimens with mRNA vaccines reported up to 95% efficacy against the original strain of the SARS-CoV-2 virus. Challenges arose with the appearance of new strains of the virus, and reports that solid organ transplant recipients may have reduced vaccination success rates after a two-dose mRNA vaccination regimen encouraged health authorities to recommend a booster in immunocompromised patients. Fabry disease is an X-linked inherited lysosomal disorder, which may lead to chronic end-stage renal disease. We report on two patients with advanced Fabry disease, renal graft and adjunctive immunosuppressive therapies who exhibited variable humoral vaccination-related immune responses against SARS-CoV-2 after three vaccine doses. The first patient developed mild COVID-19 infection, while the second patient did not seroconvert after three shots of an mRNA vaccine. Both cases emphasize that patients with Fabry disease and renal graft are susceptible to develop a weak response to COVID-19 vaccination and highlight the importance of maintaining barrier protection measures. Vaccination of family members should be encouraged to lower the risk of viral transmission to immunocompromised, transplanted patients, including vaccinated ones.

scholarly journals SARS-CoV-2-specific Humoral and Cell-mediated Immune Responses after Immunization with Inactivated COVID-19 Vaccine in Kidney Transplant Recipients (CVIM 1 Study)

2021 ◽  
Author(s):  
Jackrapong Bruminhent ◽  
Chavachol Sethaudom ◽  
Pongsathon Chaumdee ◽  
Sarinya Boongird ◽  
Sasisopin Kiertiburanakul ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Organ Transplant ◽  
Calcineurin Inhibitors ◽  
Neutralizing Antibody ◽  
Cell Mediated Immunity ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cell Responses ◽  
Clinical Trials Registry

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 non-transplant controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median age of KT recipients was 50 years (IQR, 42 to 54) and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median time since transplant was 4.5 years (IQR, 2 to 9.5). Among 35 KT patients, anti-RBD IgG titer after vaccination was not significantly different to baseline, but was significantly lower than in controls (7.8 [95%CI 0.2 to 15.5] vs 2,691 [95%CI 1,581 to 3,802], p<0.001) as well as the percentage of surrogate virus neutralizing antibody inhibition (2 [95% CI -1 to 6] vs 71 [95%CI 61 to 81], p<0.001). However, the mean of SARS-CoV-2 mixed peptides-specific T-cell responses measured by enzyme-linked immunospot assays was significantly increased compared with baseline (66 [95%CI 36 to 99] vs. 34 [95%CI 19 to 50] T-cells/10^6 PBMCs, p=0.02) and comparable to that in controls. Our findings revealed weak HMI and marginal CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccine. (Thai Clinical Trials Registry, TCTR20210226002).

scholarly journals B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients

2021 ◽  
Author(s):  
Eva Schrezenmeier ◽  
Hector Rincon-Arevalo ◽  
Ana-Luisa Stefanski ◽  
Alexander Potekhin ◽  
Henriette Staub-Hohenbleicher ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
The Third ◽  
Cellular Analysis ◽  
Cell Immunity

Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

scholarly journals Comparison of SARS-CoV-2 Antibody Response 4 Weeks After Homologous vs Heterologous Third Vaccine Dose in Kidney Transplant Recipients

2021 ◽  
Author(s):  
Roman Reindl-Schwaighofer ◽  
Andreas Heinzel ◽  
Manuel Mayrdorfer ◽  
Rhea Jabbour ◽  
Thomas M. Hofbauer ◽  
...  
Keyword(s):  
Antibody Response ◽  
Kidney Transplant ◽  
Vaccine Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Impact of a Clinical Solid Organ Transplant Pharmacist on Tacrolimus Nephrotoxicity, Therapeutic Drug Monitoring, and Institutional Revenue Generation in Adult Kidney Transplant Recipients

2016 ◽  
Vol 26 (4) ◽  
pp. 314-321 ◽  
Author(s):  
Shawn P. Griffin ◽  
Joelle E. Nelson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Kidney Transplant ◽  
Drug Monitoring ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Adult Kidney

Context: Tacrolimus requires close therapeutic drug monitoring (TDM) to ensure efficacy and minimize adverse effects. Pharmacists are uniquely positioned on transplant teams to interpret levels and recommend therapy modifications. Their impact in the immediate postoperative setting has not been described previously. Objective: To evaluate the impact of a clinical solid organ transplant pharmacist on nephrotoxicity, TDM, and revenue generation in adult kidney transplant recipients on tacrolimus. Design, Setting, and Patients: Retrospective assessment of adult kidney transplant recipients at University of Florida Health Shands Hospital. Intervention: A transplant pharmacist rounded 5 days a week and made medication recommendations on transplant recipients—including tacrolimus dose modifications based on levels. Pharmacy services were expanded to include medication reconciliation, medication counseling, and delivery of discharge medications to bedside. Main Outcome Measure: Incidence of nephrotoxicity during tacrolimus exposure. Results: Of the 70 kidney transplant recipients in the postpharmacist cohort, 18 (25.7%) experienced nephrotoxicity while on tacrolimus, compared to 18 (25%) of the 72 in the prepharmacist cohort ( P = .922). A significantly greater proportion of recipients who experienced nephrotoxicity were male, had hypertension, or experienced delayed or slow graft function. The rate of appropriately drawn tacrolimus troughs significantly increased from 23.4% to 30.3% in the postpharmacist cohort ( P < .001). The median outpatient pharmacy revenue generated per recipient significantly increased from US$345.49 (interquartile range [IQR]: 0-4727.56) to US$4834.95 per recipient (IQR: 3592.78-6224.60; P < .001). The length of stay (7 days, IQR: 6-9, vs 8 days, IQR: 6-9; P = .107) and the 30-day readmission rate were similar between groups (20.8% vs 21.4%; P = .931).

scholarly journals The Humoral Immune Response to BNT162b2 Vaccine Is Associated With Circulating CD19+ B Lymphocytes and the Naïve CD45RA to Memory CD45RO CD4+ T Helper Cells Ratio in Hemodialysis Patients and Kidney Transplant Recipients

2021 ◽  
Vol 12 ◽  
Author(s):  
Anila Duni ◽  
Georgios S. Markopoulos ◽  
Ioannis Mallioras ◽  
Haralampos Pappas ◽  
Efthymios Pappas ◽  
...  
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
Kidney Transplant ◽  
B Lymphocytes ◽  
T Helper Cells ◽  
Vaccine Dose ◽  
Transplant Recipients ◽  
T Helper ◽  
Kidney Transplant Recipients ◽  
Helper Cells

BackgroundThe humoral and cellular immune responses to SARS-COV-2 vaccination remain to be elucidated in hemodialysis (HD) patients and kidney transplant recipients (KTRs), considering their baseline immunosuppressed status. The aim of our study was to assess the associations of vaccine-induced antibody responses with circulating lymphocytes sub-populations and their respective patterns of alterations in maintenance HD patients and KTRs.Materials and MethodsWe included 34 HD patients and 54 KTRs who received two doses of the mRNA-vaccine BNT162b2. Lymphocyte subpopulations were analyzed by flow cytometry before vaccination (T0), before the second vaccine dose (T1) and 2 weeks after the second dose (T2). The anti-SARS-CoV2 antibody response was assessed at T1 and at T2.Results31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. HD patients who became seropositive following the first dose displayed higher CD19+ B lymphocytes compared to their seronegative HD counterparts. A positive correlation was established between CD19+ B cells counts and antibody titers at all time-points in both groups (p &lt; 0.001). KTRs showed higher naïve CD4+CD45RA+ T helper cells compared to HD patients at baseline and T2 whereas HD patients displayed higher memory CD45RO+ T cells compared to KTRs at T2. The naïve CD4+CD45RA to memory CD4+CD45RO+ T helper cells fraction was negatively associated with antibody production in both groups.ConclusionsOur study provides a potential conceptual framework for monitoring vaccination efficacy in HD patients and KTRs considering the correlation established between CD19+ B cells, generation of memory CD4+ T helper cells and anti SARS-CoV2 antibody response to vaccination.

scholarly journals Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jennifer L. Alejo ◽  
Jonathan Mitchell ◽  
Teresa P.-Y. Chiang ◽  
Aura T. Abedon ◽  
Brian J. Boyarsky ◽  
...  
Keyword(s):  
Antibody Response ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Fourth Dose ◽  
Solid Organ Transplant Recipients

scholarly journals SARS-CoV-2 vaccine effectiveness in immunosuppressed kidney transplant recipients

2021 ◽  
Author(s):  
Hiam Chemaitelly ◽  
Sawsan AlMukdad ◽  
Jobin Paravila Joy ◽  
Houssein H. Ayoub ◽  
HADI M. YASSINE ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Organ Transplant ◽  
Vaccine Effectiveness ◽  
Public Healthcare ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Vaccine Protection ◽  
High Level ◽  
Dose Vaccine

COVID-19 vaccine protection against infection in immunosuppressed solid organ transplant recipients is unknown but possibly weak with the low proportion of these patients mounting a robust humoral and cellular immune response after vaccination. Using a retrospective cohort study design with cross-over, we assessed vaccine effectiveness among 782 kidney transplant recipients registered at Hamad Medical Corporation, the national public healthcare provider in Qatar, where the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines have been used in the national immunization campaign. Vaccine effectiveness against any SARS-CoV-2 infection was estimated at 46.6% (95% CI: 0.0-73.7%) ≥14 days after the second dose, 66.0% (95% CI: 21.3-85.3%) ≥42 days after the second dose, and 73.9% (95% CI: 33.0-89.9%) ≥56 days after the second dose. Vaccine effectiveness against any severe, critical, or fatal COVID-19 disease was estimated at 72.3% (95% CI: 0.0-90.9%) ≥14 days after the second dose, 85.0% (95% CI: 35.7-96.5%) ≥42 days after the second dose, and 83.8% (95% CI: 31.3-96.2%) ≥56 days after the second dose. Most vaccine breakthrough infections occurred in the first few weeks after receiving the first and/or second dose. Vaccine effectiveness reached considerable levels in kidney transplant recipients, but vaccine protection mounted slowly and did not reach a high level until several weeks after the second dose.

scholarly journals Efficacy and Safety of Third Dose of the COVID-19 Vaccine among Solid Organ Transplant Recipients: A Systemic Review and Meta-Analysis

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 95
Author(s):  
Orly Efros ◽  
Roi Anteby ◽  
Mirit Halfon ◽  
Eshcar Meisel ◽  
Eyal Klang ◽  
...  
Keyword(s):  
Antibody Response ◽  
Organ Transplant ◽  
Vaccine Dose ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Efficacy And Safety ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
The Third ◽  
Solid Organ Transplant Recipients

Solid organ transplant recipients were demonstrated to have reduced antibody response to the first and second doses of the COVID-19 mRNA vaccine. This review evaluated published data on the efficacy and safety of the third dose among solid organ transplant recipients. We performed a systematic search of PubMed, EMBASE, and Web of Science to retrieve studies evaluating the efficacy of the third dose of anti-SARS-CoV-2 vaccines in adult solid organ transplant recipients. Serologic response after the third vaccine was pooled using inverse variance and generalized linear mixed and random-effects models. Seven studies met our inclusion criteria. A total of 853 patients received the third dose. Except for one randomized controlled trial, all studies were retrospective in design. Following the third COVID-19 vaccine dose, antibody response occurred in 6.4–69.2% of patients. The pooled proportion of antibody response rate after the third vaccine was 50.3% (95% confidence interval (CI): 37.1–63.5, I2 = 90%). Five papers reported the safety profile. No severe adverse events were observed after the third vaccine dose. In conclusion, a third dose of the SARS-CoV-2 mRNA vaccine in solid organ transplant recipients is associated with improved immunogenicity and appears to be safe. Nevertheless, a significant portion of patients remain seronegative.

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