Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.

[1]  A. Wallace,et al.  SARS-CoV-2 vaccine protection and deaths among US veterans during 2021 , 2021, Science.

[2]  L. Juillard,et al.  A prospective observational study for justification, safety, and efficacy of a third dose of mRNA vaccine in patients receiving maintenance hemodialysis , 2021, Kidney International.

[3]  Thomas Robert,et al.  Humoral response after SARS-COV2 vaccination in patient undergoing maintenance hemodialysis: loss of immunity, third dose and non-responders. , 2021, Nephrology, Dialysis and Transplantation.

[4]  S. Bhatt,et al.  SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion , 2021, Nature.

[5]  Jeffrey M. Wilson,et al.  Comparison of SARS-CoV-2 Antibody Response by Age Among Recipients of the BNT162b2 vs the mRNA-1273 Vaccine , 2021, JAMA network open.

[6]  L. Heylen,et al.  Comparison of SARS-CoV-2 Antibody Response Following Vaccination With BNT162b2 and mRNA-1273. , 2021, JAMA.

[7]  G. Piccoli,et al.  Humoral response to a third injection of BNT162b2 vaccine in patients on maintenance haemodialysis , 2021, Clinical kidney journal.

[8]  A. Gingras,et al.  Neutralizing antibody responses to SARS-CoV-2 variants in vaccinated Ontario long-term care home residents and workers , 2021, medRxiv.

[9]  A. Venkatakrishnan,et al.  Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence , 2021, medRxiv.

[10]  A. Davenport,et al.  Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients , 2021, The Lancet.

[11]  M. Mohty,et al.  Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies , 2021, Blood Cancer Journal.

[12]  N. Glaichenhaus,et al.  Safety and Cross-Variant Immunogenicity of a Three-dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients , 2021, EBioMedicine.

[13]  S. Omer,et al.  SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population in a Real-World Setting , 2021, Annals of Internal Medicine.

[14]  R. Bartenschlager,et al.  Neutralizing antibody response against variants of concern after vaccination of dialysis patients with BNT162b2 , 2021, Kidney International.

[15]  C. Louapre,et al.  Anti-CD20 therapies decrease humoral immune response to SARS-CoV-2 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders , 2021, Journal of Neurology, Neurosurgery, and Psychiatry.

[16]  Simon Cerny,et al.  Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine , 2021, The Lancet Regional Health - Europe.

[17]  A. Telenti,et al.  SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern , 2021, Science.

[18]  C. Courivaud,et al.  Humoral response after 3 doses of the BNT162b2 mRNA COVID-19 vaccine in patients on hemodialysis , 2021, Kidney International.

[19]  J. Achard,et al.  Humoral Response after SARS-CoV-2 mRNA Vaccination in a Cohort of Hemodialysis Patients and Kidney Transplant Recipients , 2021, Journal of the American Society of Nephrology : JASN.

[20]  H. Ulmer,et al.  The Safety and Immunogenicity of the mRNA-BNT162b2 SARS-CoV-2 Vaccine in Hemodialysis Patients , 2021, Frontiers in Immunology.

[21]  A. Sattler,et al.  Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients. , 2021, Science immunology.

[22]  B. Vogt,et al.  De novo vasculitis after mRNA-1273 (Moderna) vaccination , 2021, Kidney International.

[23]  J. Izopet,et al.  High immunogenicity of a messenger RNA based vaccine against SARS-CoV-2 in chronic dialysis patients , 2021, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[24]  L. Chan,et al.  Antibody Response to mRNA-1273 SARS-CoV-2 Vaccine in Hemodialysis Patients with and without Prior COVID-19. , 2021, Clinical journal of the American Society of Nephrology : CJASN.

[25]  M. Davenport,et al.  Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection , 2021, Nature Medicine.

[26]  I. Dasgupta,et al.  Worldwide Early Impact of COVID-19 on Dialysis Patients and Staff and Lessons Learned: A DOPPS Roundtable Discussion , 2021, Kidney Medicine.

[27]  D. Segev,et al.  Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients. , 2021, JAMA.

[28]  B. Rovin,et al.  Immune response to SARS-CoV-2 infection and vaccination in patients receiving kidney replacement therapy , 2021, Kidney International.

[29]  D. Weiner,et al.  Immunogenicity of SARS-CoV-2 Vaccine in Dialysis , 2021, medRxiv.

[30]  D. Schwartz,et al.  Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis , 2021, Clinical journal of the American Society of Nephrology : CJASN.

[31]  A. Sattler,et al.  Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis , 2021, Frontiers in Immunology.

[32]  J. Gee,et al.  Reactogenicity Following Receipt of mRNA-Based COVID-19 Vaccines. , 2021, JAMA.

[33]  A. Kribben,et al.  Humoral Response to SARS-CoV-2-Vaccination with BNT162b2 (Pfizer-BioNTech) in Patients on Hemodialysis , 2021, Vaccines.

[34]  S. Pizarro,et al.  Rapid decline of anti-SARS-CoV-2 antibodies in patients on haemodialysis: the COVID-FRIAT study , 2021, Clinical kidney journal.

[35]  M. Hernán,et al.  BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting , 2021, The New England journal of medicine.

[36]  G. Bauer,et al.  The challenge of avidity determination in SARS‐CoV‐2 serology , 2021, Journal of medical virology.

[37]  L. Rénia,et al.  COVID-19 vaccines and kidney disease , 2021, Nature Reviews Nephrology.

[38]  E. Gaspar,et al.  Avidity assay to test functionality of anti-SARS-Cov-2 antibodies , 2021, Vaccine.

[39]  R. Tedder,et al.  Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection , 2021, Kidney International.

[40]  F. Cosset,et al.  A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity , 2021, Cellular & Molecular Immunology.

[41]  J. Mascola,et al.  Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine , 2020, The New England journal of medicine.

[42]  E. Bernasconi,et al.  A data-driven approach to identify risk profiles and protective drugs in COVID-19 , 2020, Proceedings of the National Academy of Sciences.

[43]  P. Dormitzer,et al.  Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine , 2020, The New England journal of medicine.

[44]  R. Tibshirani,et al.  Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome , 2020, Science Immunology.

[45]  Lyanne M. Kieneker,et al.  COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration , 2020, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[46]  G. Chertow,et al.  Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study , 2020, The Lancet.

[47]  C. Wanner,et al.  Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe , 2020, Kidney International.

[48]  M. Beltramello,et al.  Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology , 2020, Cell.

[49]  D. Nitsch,et al.  Epidemiology of COVID-19 in an Urban Dialysis Center. , 2020, Journal of the American Society of Nephrology : JASN.

[50]  H. Keshavarz,et al.  Role of Toxoplasma gondii IgG Avidity Testing in Discriminating between Acute and Chronic Toxoplasmosis in Pregnancy , 2020, Journal of Clinical Microbiology.

[51]  G. Lippi,et al.  Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection , 2020, International Urology and Nephrology.

[52]  A. Walls,et al.  Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein , 2020, Cell.

[53]  C. Ghossein,et al.  Practical Guide to Vaccination in All Stages of CKD, Including Patients Treated by Dialysis or Kidney Transplantation. , 2020, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[54]  R. Gupta,et al.  Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I , 2019, The Journal of infectious diseases.

[55]  L. Scudeller,et al.  Comparison of the LIAISON®XL and ARCHITECT IgG, IgM, and IgG avidity assays for the diagnosis of Toxoplasma, cytomegalovirus, and rubella virus infections. , 2019, The new microbiologica.

[56]  Daniel Wrapp,et al.  Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis , 2018, Scientific Reports.

[57]  M. Forloni,et al.  Creating Insertions or Deletions Using Overlap Extension Polymerase Chain Reaction (PCR) Mutagenesis. , 2018, Cold Spring Harbor protocols.

[58]  A. Kliger Targeting Zero Infections in Dialysis: New Devices, Yes, but also Guidelines, Checklists, and a Culture of Safety. , 2018, Journal of the American Society of Nephrology : JASN.

[59]  Barney S. Graham,et al.  Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen , 2017, Proceedings of the National Academy of Sciences.

[60]  G. Parati,et al.  The systemic nature of CKD , 2017, Nature Reviews Nephrology.

[61]  R. Doms,et al.  A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection , 2015, Journal of Virology.

[62]  M. Alter,et al.  Immunogenicity of hepatitis B vaccine among hemodialysis patients: effect of revaccination of non-responders and duration of protection. , 2011, Vaccine.

[63]  Lorien S. Dalrymple,et al.  Epidemiology of acute infections among patients with chronic kidney disease. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[64]  S. Hazell Clinical utility of avidity assays. , 2007, Expert opinion on medical diagnostics.

[65]  A. Sanchez,et al.  A system for functional analysis of Ebola virus glycoprotein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[66]  R. Hehlmann Faculty Opinions recommendation of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. , 2022, Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature.