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Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients.

ABSTRACT: 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.

SUBMITTER: Sattler A

PROVIDER: S-EPMC8279581 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Impaired Humoral and Cellular Immunity after SARS-CoV2 BNT162b2 (Tozinameran) Prime-Boost Vaccination in Kidney Transplant Recipients

Project description:Novel mRNA-based vaccines have been proven powerful tools to combat the global pandemic caused by SARS-CoV2 with BNT162b2 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 prime-boost vaccination with BNT162b2. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4/39 and 1/39 transplanted individuals showed IgA and IgG seroconversion at day 8Ã‚Â±1 after booster immunization with minor changes until day 23Ã‚Â±5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared to controls and dialysis patients, 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. Signs of alloreactivity promoted by BNT162b2 were not documented within the observation period. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk to develop severe COVID-19.

| EGAS00001005280 | EGA

Improved cellular and humoral immunity upon a second BNT162b2 and mRNA-1273 boost in prime-boost vaccination no/low responders with end-stage renal disease.

Project description: Not available

| S-EPMC8489293 | biostudies-literature

Heterologous ChAdOx1 nCoV-19/BNT162b2 Prime-Boost Vaccination Induces Strong Humoral Responses among Health Care Workers.

Project description:Despite limited data on safety and immunogenicity, heterologous prime-boost vaccination is currently recommended for individuals with ChAdOx1 nCoV-19 prime immunization in certain age groups. In this prospective, single-center study we included 166 health care workers from Heidelberg University Hospital who received either heterologous ChAdOx1 nCoV-19/BNT162b2, homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination between December 2020 and May 2021. We measured anti-S1 IgG, SARS-CoV-2 specific neutralizing antibodies, and antibodies against different SARS-CoV-2 fragments 0-3 days before and 19-21 days after boost vaccination. Before boost, 55/70 (79%) ChAdOx1 nCoV-19-primed compared with 44/45 (98%) BNT162b2-primed individuals showed positive anti-S1 IgG with a median (IQR) anti-S1 IgG index of 1.95 (1.05-2.99) compared to 9.38 (6.26-17.12). SARS-CoV-2 neutralizing antibodies exceeded the threshold in 24/70 (34%) of ChAdOx1 nCoV-19-primed and 43/45 (96%) of BNT162b2-primed individuals. After boosting dose, median (IQR) anti-S1 IgG index in heterologous ChAdOx1 nCoV-19/BNT162b2 vaccinees was 116.2 (61.84-170), compared to 13.09 (7.03-29.02) in homologous ChAdOx1 nCoV-19 and 145.5 (100-291.1) in homologous BNT162b2 vaccinees. All boosted vaccinees exceeded the threshold for neutralization, irrespective of their vaccination scheme. Vaccination was well-tolerated overall. We show that heterologous ChAdOx1 nCoV-19/BNT162b2 vaccination is safe and induces a strong and broad humoral response in healthy individuals.

| S-EPMC8402499 | biostudies-literature

Heterologous prime-boost vaccination with ChAdOx1 nCoV-19 and BNT162b2.

Project description: Not available

| S-EPMC8321428 | biostudies-literature

Randomized, single blind, controlled trial to evaluate the prime-boost strategy for pneumococcal vaccination in renal transplant recipients.

Project description:UnlabelledRenal transplant recipients are at increased risk of developing invasive pneumococcal diseases but may have poor response to the 23-valent pneumococcal polysaccharide vaccine (PPV). It may be possible to enhance immunogenicity by priming with 7-valent pneumococcal conjugate vaccine (7vPnC) and boosting with PPV 1 year later. In a randomized single-blind, controlled study, adult recipients of renal transplants received either 7nPVC or PPV followed by PPV 1 year later. The vaccine response was defined as 2-fold increase in antibody concentration from baseline and an absolute post-vaccination values ≥1 µg/ml. The primary endpoint was vaccine response of the primed group (7vPnC/PPV) compared with single PPV vaccination. Antibody concentrations for 10 serotypes were measured at baseline, 8 weeks after first vaccination, before second vaccination, and 8 weeks after second vaccination. Of 320 screened patients, 80 patients were randomized and 62 completed the study. Revaccination with PPV achieved no significant increase of immune response in the 7vPnC/PPV group compared with the single PPV recipients A response to at least 1 serotype was seen in 77.1% of patients who received 7vPnC and 93.1% of patients who received PPV (P = 0.046). After second vaccination response to at least 1 serotype was seen in 87.5% patients of 7vPnC/PPV group and 87.1% patients of PPV group (non significant p). The median number of serotypes eliciting a response was 3.5 (95% CI 2.5-4.5) in the 7vPnC/PPV group versus 5 (95% CI 3.9-6.1) in the PPV group (non-significant p). Immunogenicity of pneumococcal vaccination was not enhanced by the prime-boost strategy compared with vaccination with PPV alone. Administration of a single dose of PPV should continue to be the standard of care for adult recipients of renal transplants.Trial registrationEudraCT 2007-004590-25.

| S-EPMC3460962 | biostudies-literature

Early humoral response among lung transplant recipients vaccinated with BNT162b2 vaccine.

Project description: Not available

| S-EPMC8099313 | biostudies-literature

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

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

BNT162b2 vaccination in heart transplant recipients: Clinical experience and antibody response.

Project description:BackgroundData on the safety and efficacy of SARS-CoV-2 vaccines in immunocompromised populations are sparse.MethodsWe conducted a prospective study of 77 heart transplant (HT) recipients vaccinated with two doses of BNT162b2 vaccine and monitored for adverse events following both doses, the receptor-binding domain (RBD) IgG response, and neutralizing antibodies.ResultsBNT162b2 vaccination was associated with a low rate of adverse events, characterized mostly by pain at the injection site. By a mean 41 days post second dose there were no clinical episodes of rejection, as suggested by a troponin leak or allograft dysfunction. At a mean 21 days following the second dose, IgG anti-RBD antibodies were detectable in 14 (18%) HT recipients. Immune sera neutralized SARS-CoV-2 pseudo-virus in 8 (57%) of those with IgG anti-RBD antibodies. Immunosuppressive regimen containing mycophenolic acid was associated with lower odds of an antibody response (OR = 0.12, p = 0.042).ConclusionsWhether a longer time-frame for observation of an antibody response is required after vaccination in immunosuppressed individuals remains unknown.

| S-EPMC8058049 | biostudies-literature

Lung Transplant Recipients Immunogenicity after Heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA Vaccination.

Project description:(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0-491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0-159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.

| S-EPMC9316698 | biostudies-literature

Waning humoral immune response to the BNT162b2 vaccine in heart transplant recipients over 6 months.

Project description: Not available

| S-EPMC9111345 | biostudies-literature