Immunological responses to SARS-CoV-2 vaccines in kidney transplant recipients.
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ABSTRACT:
SUBMITTER: Prendecki M
PROVIDER: S-EPMC8489877 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Immunological responses to SARS-CoV-2 vaccines in kidney transplant recipients.
Prendecki Maria M Thomson Tina T Clarke Candice L CL Martin Paul P Gleeson Sarah S De Aguiar Rute Cardoso RC Edwards Helena H Mortimer Paige P McIntyre Stacey S Mokreri Donald D Cox Alison A Pickard Graham G Lightstone Liz L Thomas David D McAdoo Stephen P SP Kelleher Peter P Willicombe Michelle M
Lancet (London, England) 20211004 10310
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Project description:Kidney transplant recipients (KTRs) have been identified as a population at increased risk for severe SARS-CoV-2 infection outcomes. This study focused on understanding the immune response of KTRs post-vaccination, specifically examining both serological and cellular responses to the SARS-CoV-2 vaccine. Thirteen individuals, including seven KTRs and six healthy donors, were evaluated for antibody levels and T cell responses post-vaccination. The study revealed that KTRs had significantly lower serological responses, including reduced anti-receptor binding domain (RBD) binding antibodies and neutralizing antibodies against the Wuhan, Delta, and Omicron BA.2 strains. Additionally, KTRs demonstrated weaker CD8 T cell cytotoxic responses and lower Th1 cytokine secretion, particularly IFN-γ, after stimulation with variant spike peptide pools. These findings highlight the compromised immunity in KTRs post-vaccination and underscore the need for tailored strategies to bolster immune responses in this vulnerable group. Further investigations are warranted into the mechanisms underlying reduced vaccine efficacy in KTRs and potential therapeutic interventions.ImportanceSome studies have revealed that KTRs had lower serological response against SARS-CoV-2 than healthy people. Nevertheless, limited studies investigate the cellular response against SARS-CoV-2 in KTRs receiving SARS-CoV-2 vaccines. Here, we found that KTRs have lower serological and cellular responses. Moreover, we found that KTRs had a significantly lower IFN-γ secretion than healthy individuals when their PBMCs were stimulated with SARS-CoV-2 spike peptide pools. Thus, our findings suggested that additional strategies are needed to enhance KTR immunity triggered by the vaccine.
| S-EPMC11237705 | biostudies-literature
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| S-EPMC7790204 | biostudies-literature
Project description:Kidney transplant recipients (KTRs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have an increased risk of mortality compared with the general population and hemodialysis patients. As these patients are immunosuppressed, it might seem obvious to attribute this excess mortality to the impaired immunity induced by immunosuppression. In line with this reasoning is the low immune response, both cellular and humoral, that KTRs mount in response to the anti-SARS-CoV-2 vaccine; however, acute respiratory distress syndrome associated with coronavirus disease 2019 is triggered by a state of inflammation and cytokine release syndrome that lead to pulmonary damage and increased mortality. In that context, immunosuppressive treatment dampening the immune response could, in theory, be potentially beneficial. This review aims at analyzing the current knowledge on the impact of immunosuppressive treatment on mortality in SARS-CoV-2-infected KTRs, the optimal management of immunosuppression in the coronavirus disease 2019 era, and the vaccine response and management in immunosuppressed KTRs.
| S-EPMC8843373 | biostudies-literature
Project description:Dialysis patients and kidney transplant (KTX) recipients suffer from an impaired immune system and show a decreased response to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination. We performed a retrospective analysis of 1505 serological SARS-CoV-2 measurements obtained from 887 dialysis patients and 86 KTX recipients. The results were separated by patient subgroups (dialysis/KTX) as well as SARS-CoV-2 status. The latter criterion included SARS-CoV-2-naïve patients with or without COVID-19 vaccination and convalescent patients receiving a booster shot. Serologies of 27 vaccinated healthy individuals served as the reference group. Vaccine-induced cellular immune response was quantified by an interferon-γ release assay in 32 KTX recipients. We determined seroconversion rates of 92.6%, 93.4%, and 71.4% in dialysis patients vaccinated with either BNT162b2, mRNA-1273, or AZD1222, respectively. Vaccination-induced anti-SARS-CoV-2 antibody titers were lower in dialysis patients compared to healthy individuals, and vaccination with mRNA-1273 induced higher titers than BNT162b2. The initial seroconversion rate was 39.5% in KTX recipients vaccinated with BNT162b2. A linear regression model identified medication with mycophenolate-mofetil/mycophenolic acid as an independent risk factor for missing seroconversion. Within a cohort of 32 KTX recipients, cellular and humoral immune reactivity to SARS-CoV-2 was detectable in three patients only. Conclusively, vaccine-induced seroconversion rates were similar in dialysis patients compared to healthy individuals but were strongly impaired in KTX recipients. Anti-SARS-CoV-2 IgG titers elicited by double active immunization were significantly lower in both cohorts compared to healthy individuals, and immune responses to vaccination vanished quickly.
| S-EPMC8779774 | biostudies-literature
Project description:Kidney transplant recipients (KTRs) are reported to have worse outcomes with COVID-19, and empiric reduction of T-cell directed immunosuppression has been pursued. Here we evaluated the peripheral blood transcriptome of 64 KTRs either during and after acute COVID-19. We identified transcriptomic signatures of suppression of adaptive T-cell responses which significantly associated with disease severity and showed evidence of recovery after acute disease. These findings were consistent with public data from non-KTR cohorts.
2022-07-15 | GSE195796 | GEO
Project description:BackgroundKidney transplant recipients (KTR) are at high risk for severe COVID-19 and have demonstrated poor response to vaccination, making it unclear whether successive vaccinations offer immunity and protection.MethodsWe conducted a serologically guided interventional study where KTR patients that failed to seroconvert were revaccinated and also monitored seroconversion of KTR following the Norwegian vaccination program. We analysed IgG anti-RBD Spike responses from dose 2 (n = 432) up to after the 6th (n = 37) mRNA vaccine dose. The frequency and phenotype of Spike-specific T and B cell responses were assessed in the interventional cohort after 3-4 vaccine doses (n = 30). Additionally, we evaluated the Specific T and B cell response to breakthrough infection (n = 32), measured inflammatory cytokines and broadly cross-neutralizing antibodies, and defined the incidence of COVID-19-related hospitalizations and deaths. The Norwegian KTR cohort has a male dominance (2323 males, 1297 females), PBMC were collected from 114 male and 78 female donors.FindingsAfter vaccine dose 3, most KTR developed Spike-specific T cell responses but had significantly reduced Spike-binding B cells and few memory cells. The B cell response included a cross-reactive subset that could bind Omicron VOC, which expanded after breakthrough infection (BTI) and gave rise to a memory IgG+ B cell response. After BTI, KTR had increased Spike-specific T cells, emergent non-Spike T and B cell responses, and a systemic inflammatory signature. Late seroconversion occurred after doses 5-6, but 38% (14/37) of KTR had no detectable immunity even after multiple vaccine doses.InterpretationBoosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population.FundingCEPI and internal funds.
| S-EPMC10585642 | biostudies-literature
Project description: Not available
| S-EPMC8280658 | biostudies-literature
Project description:PurposeAdvanced age is associated with an impaired humoral immune response to SARS-CoV-2 mRNA vaccination in kidney transplant recipients (KTR). The mechanisms are, however, poorly understood. Frailty syndrome assessment may determine the most vulnerable population.MethodsThis study is a secondary analysis of a prospective study (NCT04832841) regarding seroconversion after BNT162b2 vaccination, including 101 SARS-CoV-2 naïve KTR 70 years and older. The Fried frailty components were evaluated, and antibodies against S1 and S2 subunits of SARS-CoV-2 were examined > 14 days after the second dose of BNT162b2 vaccine.ResultsSeroconversion was observed in 33 KTR. Male gender, eGFR, MMF-free immunosuppression, and a lower frailty score were associated with higher seroconversion rates in univariable regression. Concerning frailty components, physical inactivity had the most negative effect on seroconversion (OR = 0.36, 95% CI 0.14-0.95, p = 0.039). In a multivariable regression adjusted for eGFR, MMF-free immunosuppression, time from transplant and gender, pre-frail (OR = 0.27, 95% CI 0.07-1.00, p = 0.050), and frail status (OR = 0.14, 95% CI 0.03-0.73, p = 0.019) were associated with an increased risk of unresponsiveness to SARS-CoV-2 vaccines.ConclusionFrailty was associated with an impaired humoral response to SARS-CoV-2 mRNA vaccination in older SARS-CoV-2 naïve KTR.Trail registrationThis study is registered under the identifier NCT04832841 on ClinicalTrials.gov.
| S-EPMC10081301 | biostudies-literature
Project description:Activated T follicular helper (aTfh) cells are likely important in host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. We characterized the immune responses of aTfh cells to the second (D2) and third (booster; D3) doses of an mRNA vaccine in the peripheral blood of 40 kidney transplant recipients (KTRs) and 17 healthy control volunteers (HCs). A significant increase in SARS-CoV-2-specific IgG antibody was seen after D3 in the KTRs; nonetheless, the levels after D2 and D3 were significantly lower than in the HCs. After D2, dramatic increases in activated CD45RA-CXCR5+ICOS+PD1+ circulating Tfh (acTfh) cells were observed in the HCs, as well as the seropositive patients among the KTRs, when compared with the seronegative patients among the KTRs. Unlike the HCs, KTRs had less prominent immune responses, including the acTfh and T cells that produce interferon gamma, tumor necrosis factor alpha, and interleukin 21. In addition, the increase in acTfh cells was significantly associated with anti-IgG antibody levels after D3. These results indicate impaired SARS-CoV-2-specific responses via acTfh cells in KTRs, and they suggest that acTfh cells in peripheral blood may play an important role in antibody maintenance following SARS-CoV-2 mRNA vaccination.
| S-EPMC11490627 | biostudies-literature
Project description:The immunological imprint after two doses of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) mRNA vaccination for patients after kidney transplantation (KTx) remain unclear. This study included KTx recipients and volunteer healthy controls (HCs) who received two doses of SARS-CoV-2 mRNA vaccine (Pfizer BioNTech) from January 2021 to December 2021. We analyzed safety within 21 days after each vaccination dose and compared the immune response in peripheral blood mononuclear cells (PBMCs) between the two groups. No graft rejection was observed throughout this study. Adverse events were generally observed within 5 days. The KTx group exhibited a significantly lower degree of symptoms between doses 1 and 2 (P < 0.001). Increases in activated subsets of T and B cells expressing human leukocyte antigen (HLA)-DR and/or CD38 were observed in the HC group after dose 2 (both P < 0.001), with the greatest increases in HLA-DR+CD8+ T cells and CD38+CD19+ B cells (P = 0.042 and P = 0.031, respectively). In addition, PD1+CD8+ T cells-but not PD1+CD4+ T cells-increased significantly in the HC group (P = 0.027). In the KTx group, however, activated HLA-DR+, CD38+, and PD1+ cells remained at baseline levels. Immunoglobulin (Ig)G against SARS-CoV-2 was detected in only four KTx recipients (13.3%) after dose 2 (P < 0.001). Multivariate logistic regression analyses revealed that ΔHLA-DR+CD8+ T cells and ΔCD38+CD19+ B cells were significantly associated with IgG formation (both P = 0.02). SARS-CoV-2 mRNA vaccine generates impaired cellular and humoral immunity for KTx recipients. Results indicate the need for modified vaccination strategies in immunocompromised KTx recipients.
| S-EPMC9553995 | biostudies-literature