Immune Response to COVID-19 mRNA Vaccination in Previous Nonresponder Kidney Transplant Recipients After Short-term Withdrawal of Mycophenolic Acid 1 and 3 Months After an Additional Vaccine Dose

Kühn, Tessa; Speer, Claudius; Morath, Christian; Bartenschlager, Marie; Kim, Heeyoung; Beimler, Jörg; Buylaert, Mirabel; Nußhag, Christian; Kälble, Florian; Reineke, Marvin; Töllner, Maximilian; Klein, Katrin; Blank, Antje; Parthé, Sylvia; Schnitzler, Paul; Zeier, Martin; Süsal, Caner; Bartenschlager, Ralf; Tran, Thuong Hien; Schaier, Matthias; Benning, Louise

doi:10.1097/tp.0000000000004516

Cited by 15 publications

(17 citation statements)

References 45 publications

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“…In this study, 10 KTRs showed a SARS-CoV-2 breakthrough infection with a predominantly mild course of COVID-19, which is in line with others reporting of predominantly mild courses of COVID-19 in three-times vaccinated healthy subjects (11,42,73,74) and KTRs (54,61). Interestingly, we observed evenly distributed cases of breakthrough infections in hoVac compared to heVac KTRs and KTRs with a breakthrough infection had significantly lower spike S1-specific T-cell responses as compared to uninfected KTRs.…”

Section: Discussionsupporting

confidence: 92%

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Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients

et al. 2023

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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.

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Section: Discussionsupporting

confidence: 92%

“…Previous studies that explored cellular SARS-CoV-2-specific immunity in KTRs mainly focused on assays predominantly analyzing IFN-g-related immune responses (17,18,61). This approach might lead to an underestimation of the SARS-CoV-2specific T-cell immunity in KTRs, when, e.g., IL-2-related immune responses are not detected (62).…”

Section: Discussionmentioning

confidence: 99%

Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients

et al. 2023

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“…Results on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific humoral response as well as safety data regarding development of donor-specific antibodies (DSAs) and changes in donor-derived cell-free DNA (dd-cfDNA) in patients with MPA withdrawal were published previously. 12,13 This additional, post hoc analysis focuses on changes in TTV load in long-term KTRs with short-term changes in immunosuppressive therapy.…”

Section: Methodsmentioning

confidence: 99%

Quantification of Torque Teno Virus Load to Monitor Short-term Changes in Immunosuppressive Therapy in Kidney Transplant Recipients

Benning,

Reineke,

Bundschuh

et al. 2023

Transplantation

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Background. Quantification of torque teno virus (TTV) has been proposed as a surrogate parameter to monitor immunocompetence in kidney transplant recipients (KTRs) early after transplantation. However, its use in monitoring short-term changes of immunosuppression in KTRs late after transplantation requires further investigation. Methods. In this post hoc analysis, we quantified TTV load in sera of 76 KTRs, with 43 pausing mycophenolic acid (MPA) 1 wk before to 4 wk after COVID-19 vaccination to increase vaccine response. TTV load was quantified before, 4 wk, and 3 mo postvaccination. Results were compared to 33 KTRs with continued standard immunosuppressive therapy and with 18 hemodialysis as well as 18 healthy control subjects. Results. TTV load before vaccination was with a median (interquartile range) of 1.39 × 104 copies/milliliter (c/mL) (9.17 × 101–2.66 × 105 c/mL) highest in KTRs compared to 1.73 × 103 c/mL (1.07 × 103–1.31 × 104 c/mL) in hemodialysis patients and 1.53 × 102 c/mL (6.38–1.29 × 103 c/mL) in healthy controls. In KTRs with MPA withdrawal, TTV load decreased significantly from a median (interquartile range) of 1.11 × 104 c/mL (4.75 × 102–1.92 × 105 c/mL) to 5.24 × 103 c/mL (6.92 × 102–6.91 × 104 c/mL) 4–5 wk after initiation of MPA withdrawal (P = 0.003). In patients with MPA withdrawal, TTV load was significantly inversely correlated with COVID-19 or SARS-CoV-2–specific antibodies 4 wk and 3 mo postvaccination (P = 0.009 and P = 0.004). Conclusions. TTV load reflects changes in immunosuppressive therapy even late after transplantation, supporting its use to monitor immunocompetence in KTRs.

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“…Our result matches those of other investigations that showed waning humoral immunity in KTRs after vaccination. 33–35 Therefore, the recommendation for booster vaccine doses for KTRs is of high importance, 36–38 especially since vaccination is associated with decreased risk of SARS-CoV-2 infection in KTRs. 39 …”

Section: Discussionmentioning

confidence: 99%

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines

Mahallawi¹,

Alharbi²,

Aloufi³

et al. 2023

IDR

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Background Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs’ compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies. Methods A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies. Results The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p<0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3–3]) and seven months (2.4 [1.7–2.6]) after vaccination (p<0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p<0.01). IgG levels also decreased significantly in KTRs with a transplant of >10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p<0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3–3]) and seven months (2.4 [1.9–2.6]) after vaccination (p<0.01). Conclusion KTRs’ humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.

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Immune Response to COVID-19 mRNA Vaccination in Previous Nonresponder Kidney Transplant Recipients After Short-term Withdrawal of Mycophenolic Acid 1 and 3 Months After an Additional Vaccine Dose

Cited by 15 publications

References 45 publications

Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients

Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients

Quantification of Torque Teno Virus Load to Monitor Short-term Changes in Immunosuppressive Therapy in Kidney Transplant Recipients

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines

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