Humoral Response to Heterologous SARS-CoV-2 Vaccination in Kidney Transplant Patients Is Heterogeneous and Dose Dependent.
Ontology highlight
ABSTRACT:
SUBMITTER: Seija M
PROVIDER: S-EPMC9098806 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Publications
Humoral Response to Heterologous SARS-CoV-2 Vaccination in Kidney Transplant Patients Is Heterogeneous and Dose Dependent.
Seija Mariana M Rammauro Florencia F Noboa Javier J Santiago José J Orihuela Natalia N Zulberti Catherine C Machado Danilo D Recalde Cecilia C Astesiano Rossana R Yandián Federico F Frantchez Victoria V Guerisoli Ana A Morra Álvaro Á Cassinelli Daniela D Coelho Cecilia C de Aramburu Belén B González-Severgnini Paulina P Moreno Romina R Pippolo Aldana A López Gabriela G Lemos Mónica M Somariva Lorena L López Eliana E Fumero Soledad S Orihuela Carla C Suárez Ana Laura AL Rodríguez Rosalía R Acuña Gonzalo G Rabaza Victoria V Perg Nancy N Cordero Rossana R Reisfeld Cristina C Olivera Paula P Montero Paola P Nogueira Cecilia C Nalerio Catheryn C Orihuela Sergio S Curi Lilián L Bugstaller Ema E Pritsch Otto O Nin Marcelo M Noboa Oscar O Bianchi Sergio S
Kidney international reports 20220513 8
Similar Datasets
Project description: Not available
| S-EPMC9038233 | biostudies-literature
Project description:Data on the immune response to SARS-CoV-2 in kidney transplant recipients are scarce. Thus, we conducted a single-center observational study to assess the anti-SARS-CoV-2 IgG seroprevalence in outpatient kidney transplant recipients (KTR; n = 1037) and healthcare workers (HCW; n = 512) during the second wave of the COVID-19 pandemic in fall 2020 and evaluated the clinical variables affecting antibody levels. Antibodies against S1 and S2 subunit of SARS-CoV-2 were evaluated using immunochemiluminescent assay (cut off 9.5 AU/ml, sensitivity of 91.2% and specificity of 90.2%). Anti-SARS-CoV-2 IgG seroprevalence was lower in KTR than in HCW (7% vs. 11.9%, p = .001). Kidney transplant recipients with SARS-CoV-2 infection were younger (p = .001) and received CNI-based immunosuppression more frequently (p = .029) than seronegative KTR. Anti-SARS-CoV-2 IgG positive symptomatic KTR had a higher BMI (p = .04) than asymptomatic KTR. Interestingly, anti-SARS-CoV-2 IgG levels were higher in KTR than in HCW (median 31 AU/ml, IQR 17-84 vs. median 15 AU/ml, IQR 11-39, p < .001). The presence of moderate to severe symptoms in KTR was found to be the only independent factor affecting IgG levels (Beta coefficient = 41.99, 95% CI 9.92-74.06, p = .011) in the multivariable model. In conclusion, KTR exhibit a well-preserved symptom-dependent humoral response to SARS-CoV-2 infection.
| S-EPMC9906442 | biostudies-literature
Project description:Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses, counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo-activated programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients.
| S-EPMC9090237 | biostudies-literature
Project description:The immunogenicity of SARS-CoV-2 vaccines in kidney transplant recipients is limited, resulting in inadequately low serological response rates and low immunoglobulin (Ig) levels, correlating with reduced protection against death and hospitalization from COVID-19. We retrospectively examined the time course of anti-SARS-CoV-2 Ig antibody levels after up to five repeated vaccinations in 644 previously nonresponding kidney transplant recipients. Using anti SARS-CoV-2 IgG/IgA ELISA and the total Ig ECLIA assays, we compared antibody levels at 1 month with levels at 2 and 4 months, respectively. Additionally, we correlated the measurements of the used assays. Between 1 and 2 months, and between 1 and 4 months, mean anti-SARS-CoV-2 Ig levels in responders decreased by 14% and 25%, respectively, depending on the assay. Absolute Ig values and time course of antibody levels showed high interindividual variability. Ig levels decreased by at least 20% in 77 of 148 paired samples with loss of sufficient serological protection over time occurring in 18 out of 148 (12.2%). IgG ELISA and total Ig ECLIA assays showed a strong positive correlation (Kendall's tau = 0.78), yet the two assays determined divergent results in 99 of 751 (13.2%) measurements. IgG and IgA assays showed overall strong correlation but divergent results in 270 of 1.173 (23.0%) cases and only weak correlation of antibody levels in positive samples. Large interindividual variability and significant loss of serological response after 4 months supports repeated serological sampling and consideration of shorter vaccination intervals in kidney transplant recipients.
| S-EPMC9224612 | biostudies-literature
Project description:Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2, with BNT162b2 (trade name: Comirnaty) efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine-induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after the standard second vaccination dose. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4 of 39 and 1 of 39 transplanted individuals showed IgA and IgG seroconversion at day 8 ± 1 after booster immunization, with minor changes until day 23 ± 5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared with those in controls and dialysis patients and this was accompanied by a broad impairment in effector cytokine production, memory differentiation, and activation-related signatures. Spike-specific CD8+ T cell responses were less abundant than their CD4+ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Promotion of anti-HLA antibodies or acute rejection was not detected after vaccination. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk of developing severe COVID-19.
| S-EPMC8279581 | biostudies-literature
Project description: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.
| S-EPMC8708799 | biostudies-literature
Project description:BackgroundKidney transplant recipients (KTRs) are at high risk for a severe course of coronavirus disease 2019 (COVID-19); thus, effective vaccination is critical. However, the achievement of protective immunogenicity is hampered by immunosuppressive therapies. We assessed cellular and humoral immunity and breakthrough infection rates in KTRs vaccinated with homologous and heterologous COVID-19 vaccination regimens.MethodWe performed a comparative in-depth analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses using multiplex Fluorospot assays and SARS-CoV-2-specific neutralizing antibodies (NAbs) between three-times homologously (n = 18) and heterologously (n = 8) vaccinated KTRs.ResultsWe detected SARS-CoV-2-reactive T cells in 100% of KTRs upon third vaccination, with comparable frequencies, T-cell expression profiles, and relative interferon γ and interleukin 2 production per single cell between homologously and heterologously vaccinated KTRs. SARS-CoV-2-specific NAb positivity rates were significantly higher in heterologously (87.5%) compared to homologously vaccinated (50.0%) KTRs (P < 0.0001), whereas the magnitudes of NAb titers were comparable between both subcohorts after third vaccination. SARS-CoV-2 breakthrough infections occurred in equal numbers in homologously (38.9%) and heterologously (37.5%) vaccinated KTRs with mild-to-moderate courses of COVID-19.ConclusionOur data support a more comprehensive assessment of not only humoral but also cellular SARS-CoV-2-specific immunity in KTRs to provide an in-depth understanding about the COVID-19 vaccine-induced immune response in a transplant setting.
| S-EPMC10102365 | biostudies-literature
Project description:BackgroundHomologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies.MethodsCOV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, and avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in blood samples up to 2 weeks before (T1) and 2-12 weeks following secondary immunization (T2).ResultsInitial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV-19 413 ± 461 BAU/ml, both p < .001; spike-induced T-cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV-19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T-cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T-cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T-cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2.ConclusionsInterdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T-cell activation is unlikely to compensate for poor humoral responses.
| S-EPMC9111248 | biostudies-literature
Project description: Not available
| S-EPMC8503972 | biostudies-literature
Project description: Not available
| S-EPMC8842381 | biostudies-literature