Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis

TY - JOUR

T1 - Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis

AU - Schrezenmeier, Eva

AU - Bergfeld, Leon

AU - Hillus, David

AU - Lippert, Joerg-Detlev

AU - Weber, Ulrike

AU - Tober-Lau, Pinkus

AU - Landgraf, Irmgard

AU - Schwarz, Tatjana

AU - Kappert, Kai

AU - Stefanski, Ana-Luisa

AU - Sattler, Arne

AU - Kotsch, Katja

AU - Dörner, Thomas

AU - Sander, Leif Erik

AU - Budde, Klemens

AU - Halleck, Fabian

AU - Kurth, Florian

AU - Corman, Victor Max

AU - Choi, Mira

N1 - Copyright © 2021 Schrezenmeier, Bergfeld, Hillus, Lippert, Weber, Tober-Lau, Landgraf, Schwarz, Kappert, Stefanski, Sattler, Kotsch, Dörner, Sander, Budde, Halleck, Kurth, Corman and Choi.

PY - 2021

Y1 - 2021

N2 - Patients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). This observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period until three weeks after the second dose and 32 patients were further analyzed at week 10. Serum samples were analyzed by SARS-CoV-2 specific IgG and IgA antibodies ~1, ~3-4 and ~10 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at ~3-4 weeks by an interferon-gamma release assay (IGRA). Antibody and T cell outcomes at this timepoint were compared to a group of 44 elderly patients not on dialysis, after immunization with Tozinameran. Median age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29-71.67) developed SARS-CoV-2-IgG antibodies at the first sampling, whereas 32/36 patients (88.9%, 95%CI: 73.00-96.38) demonstrated IgG detection at the second sampling. In a longitudinal follow-up at ~10 weeks after the second dose, the proportion of dialysis patients reactive for anti-SARS-CoV-2-IgG decreased to 27/32 (84.37%, 95%CI: 66.46-94.10) The proportion of anti-SARS-CoV-2 S1 IgA decreased from 33/36 (91.67%; 95%CI: 76.41-97.82) at weeks 3-4 down to 19/32 (59.38; 95%CI: 40.79-75.78). Compared to a cohort of vaccinees with similar age but not on chronic dialysis seroconversion rates and antibody titers were significantly lower. SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53-82.68) compared to 42/44 (93.3%, 95%CI: 76.49-98.84) in controls of similar age. Patients on dialysis demonstrate a delayed, but robust immune response three to four weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.

AB - Patients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). This observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period until three weeks after the second dose and 32 patients were further analyzed at week 10. Serum samples were analyzed by SARS-CoV-2 specific IgG and IgA antibodies ~1, ~3-4 and ~10 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at ~3-4 weeks by an interferon-gamma release assay (IGRA). Antibody and T cell outcomes at this timepoint were compared to a group of 44 elderly patients not on dialysis, after immunization with Tozinameran. Median age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29-71.67) developed SARS-CoV-2-IgG antibodies at the first sampling, whereas 32/36 patients (88.9%, 95%CI: 73.00-96.38) demonstrated IgG detection at the second sampling. In a longitudinal follow-up at ~10 weeks after the second dose, the proportion of dialysis patients reactive for anti-SARS-CoV-2-IgG decreased to 27/32 (84.37%, 95%CI: 66.46-94.10) The proportion of anti-SARS-CoV-2 S1 IgA decreased from 33/36 (91.67%; 95%CI: 76.41-97.82) at weeks 3-4 down to 19/32 (59.38; 95%CI: 40.79-75.78). Compared to a cohort of vaccinees with similar age but not on chronic dialysis seroconversion rates and antibody titers were significantly lower. SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53-82.68) compared to 42/44 (93.3%, 95%CI: 76.49-98.84) in controls of similar age. Patients on dialysis demonstrate a delayed, but robust immune response three to four weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Neutralizing/blood

KW - Antibodies, Viral/blood

KW - BNT162 Vaccine

KW - COVID-19/blood

KW - COVID-19 Vaccines/immunology

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Immunity

KW - Immunogenicity, Vaccine

KW - Immunoglobulin A/blood

KW - Immunoglobulin G/blood

KW - Longitudinal Studies

KW - Male

KW - Middle Aged

KW - Renal Dialysis

KW - SARS-CoV-2/genetics

KW - Spike Glycoprotein, Coronavirus/immunology

KW - T-Lymphocytes/immunology

KW - Vaccination/methods

U2 - 10.3389/fimmu.2021.690698

DO - 10.3389/fimmu.2021.690698

M3 - SCORING: Journal article

C2 - 34276681

VL - 12

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

M1 - 690698

ER -