Louise Benning1, Christian Morath1, Marie Bartenschlager2, Christian Nusshag1, Florian Kälble1, Mirabel Buylaert1, Matthias Schaier1, Jörg Beimler1, Katrin Klein1, Julia Grenz1, Paula Reichel1, Asa Hidmark1, Gerald Ponath1, Maximilian Töllner1, Marvin Reineke1, Susanne Rieger3, Burkhard Tönshoff3, Paul Schnitzler4, Martin Zeier1, Caner Süsal5,6, Ralf Bartenschlager2,7,8, Claudius Speer9,10. 1. Department of Nephrology, University of Heidelberg, Heidelberg, Germany. 2. Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany. 3. Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany. 4. Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany. 5. Institute of Immunology, University of Heidelberg, Heidelberg, Germany. 6. Transplant Immunology Research Center of Excellence, Koç Üniversitesi Hastanesi, Istanbul, Turkey. 7. German Center for Infection Research, Heidelberg Partner Site, Heidelberg, Germany. 8. Division of Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany. 9. Department of Nephrology, University of Heidelberg, Heidelberg, Germany claudius.speer@med.uni-heidelberg.de. 10. Molecular Medicine Partnership Unit Heidelberg, European Molecular Biology Laboratory, Heidelberg, Germany.
Abstract
BACKGROUND AND OBJECTIVES: Antibody response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is impaired in kidney transplant recipients. Emerging variants, such as B.1.617.2 (δ), are of particular concern because of their higher transmissibility and partial immune escape. Little is known about protection against these variants in immunocompromised patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective two-center study, antispike 1 IgG and surrogate neutralizing antibodies were measured in 173 kidney transplant recipients and 166 healthy controls with different vaccination schedules. In addition, different SARS-CoV-2 epitope antibodies from 135 vaccinated kidney transplant recipients were compared with antibodies in 25 matched healthy controls after second vaccination. In 36 kidney transplant recipients with seroconversion, neutralization against B.1.1.7 (α), B.1.351 (β), and B.1.617.2 (δ) was determined on VeroE6 cells and compared with neutralization in 25 healthy controls. RESULTS: Kidney transplant recipients had significantly lower seroconversion rates compared with healthy controls. After the second vaccination, antispike 1, antireceptor-binding domain, and surrogate neutralizing antibodies were detectable in 30%, 27%, and 24% of kidney transplant recipients, respectively. This compares with 100%, 96%, and 100% in healthy controls, respectively (P<0.001). Neutralization against B.1.1.7 was detectable in all kidney transplant recipients with seroconversion, with a median serum dilution that reduces infection of cells by 50% of 80 (interquartile range, 80-320). In contrast, only 23 of 36 (64%) and 24 of 36 (67%) kidney transplant recipients showed neutralization against B.1.351 and B.1.617.2, respectively, with median serum dilutions that reduce infection of cells by 50% of 20 (interquartile range, 0-40) and 20 (interquartile range, 0-40), respectively. Neutralization against different variants was significantly higher in healthy controls (P<0.001), with all patients showing neutralization against all tested variants. CONCLUSIONS: Seroconverted kidney transplant recipients show impaired neutralization against emerging variants of concern after standard two-dose vaccination. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Observational study to assess the SARS-CoV-2 specific immune response in kidney transplant recipients (COVID-19 related immune response), DRKS00024668.
BACKGROUND AND OBJECTIVES: Antibody response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is impaired in kidney transplant recipients. Emerging variants, such as B.1.617.2 (δ), are of particular concern because of their higher transmissibility and partial immune escape. Little is known about protection against these variants in immunocompromised patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective two-center study, antispike 1 IgG and surrogate neutralizing antibodies were measured in 173 kidney transplant recipients and 166 healthy controls with different vaccination schedules. In addition, different SARS-CoV-2 epitope antibodies from 135 vaccinated kidney transplant recipients were compared with antibodies in 25 matched healthy controls after second vaccination. In 36 kidney transplant recipients with seroconversion, neutralization against B.1.1.7 (α), B.1.351 (β), and B.1.617.2 (δ) was determined on VeroE6 cells and compared with neutralization in 25 healthy controls. RESULTS: Kidney transplant recipients had significantly lower seroconversion rates compared with healthy controls. After the second vaccination, antispike 1, antireceptor-binding domain, and surrogate neutralizing antibodies were detectable in 30%, 27%, and 24% of kidney transplant recipients, respectively. This compares with 100%, 96%, and 100% in healthy controls, respectively (P<0.001). Neutralization against B.1.1.7 was detectable in all kidney transplant recipients with seroconversion, with a median serum dilution that reduces infection of cells by 50% of 80 (interquartile range, 80-320). In contrast, only 23 of 36 (64%) and 24 of 36 (67%) kidney transplant recipients showed neutralization against B.1.351 and B.1.617.2, respectively, with median serum dilutions that reduce infection of cells by 50% of 20 (interquartile range, 0-40) and 20 (interquartile range, 0-40), respectively. Neutralization against different variants was significantly higher in healthy controls (P<0.001), with all patients showing neutralization against all tested variants. CONCLUSIONS: Seroconverted kidney transplant recipients show impaired neutralization against emerging variants of concern after standard two-dose vaccination. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Observational study to assess the SARS-CoV-2 specific immune response in kidney transplant recipients (COVID-19 related immune response), DRKS00024668.
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