A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients

Novel mRNA-based vaccines have been proven powerful tools to combat the global pandemic caused by SARS-CoV2 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 4/39 and 1/39 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 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. 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 to develop severe COVID-19.

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Section: Introductionmentioning

confidence: 99%

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

Sattler¹,

Schrezenmeier

Weber

et al. 2021

Journal of Clinical Investigation

228

235

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“…Therefore, accounting for all SARS-CoV2 vaccines authorized thus far, information on kinetics and quality of specific immunity in kidney transplant and hemodialysis patients remains scarce. Experience from influenza A/H1N1 (11,12) and hepatitis B vaccination trials (13,14) indicate lower humoral responder rates in both patient groups, likely resulting from combined impairment of early memory B and T cell formation (15). To provide pioneering data on mRNA vaccine-specific adaptive immunity, we quantified humoral and cellular responses induced by BNT162b2 in healthy controls as compared to patients on dialysis and kidney transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

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

Sattler

Schrezenmeier

Weber

et al. 2021

Preprint

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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 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 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.

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“…Fendrix TM has always shown a high level of immunogenicity. On the other hand, further vaccines are being produced and offer promising results [22]. A major result of the current study was the assessment of predictive factors, which could play impact on the immune response to HBV-AS04.…”

Section: Discussionmentioning

confidence: 99%

HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population

Fabrizi¹,

Cerutti²,

Nardelli³

et al. 2020

Clinics and Research in Hepatology and Gastroenterology

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Background: Patients with chronic kidney disease have a poor response to hepatitis B vaccine due to the immunodeficiency conferred from chronic uremia. A recombinant HB vaccine containing an improved adjuvant system AS04 (HBV-AS04) has been manufactured but scarce evidence exists on HBV-AS04 use among patients with CKD. Aim: To assess efficacy and safety of an adjuvanted recombinant vaccine (HBV-AS04) in a large cohort of CKD patients at pre-dialysis stage (with susceptibility to HBV infection). Methods: Patients were prospectively enrolled to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 1, 2, 3, and 4. Anti-HBs surface antibody concentrations were tested at intervals of 1, 2, 3, 4, and 12 months. Multivariate analyses were performed to assess the parameters, which predicted immunologic response to HBV-AS04 vaccine. Results: One hundred and seven patients were included and 102 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers ≥ 10 mIU/mL) was 95% (97/102) (mean anti-HBs antibody titers, 688.9 ± 385 mIU/mL), according to per-protocol analysis. Serum haemoglobin levels were greater in responder than non-or low-responder patients to HBV-AS04 (P = 0.04) and this was confirmed by multivariate analysis. The seroprotection rate at month 50 was 88% (30/34) with lower anti-HBs antibody titers (218.5 ± 269.6 mIU/mL, P = 0.001). No major side effects were observed. Conclusions: Our prospective study performed in a real-world setting showed a high immunogenicity and safety of HBV-AS04 vaccine in patients with CKD not yet on maintenance dialysis. Studies provided with longer follow-ups are under way to assess the durability of seroprotection in responders.

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A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients

Cited by 25 publications

References 28 publications

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

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

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

HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population

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