Waning humoral response 6 months after SARS-CoV-2 vaccination with the mRNA-BNT162b2 vaccine in hemodialysis patients: time for a boost
Authors: Tamara Davidovic, Judith Schimpf, Armin Abbassi-Nik, Richard Stockinger, Hannelore Sprenger-Mähr, Karl Lhotta, Emanuel Zitt
Journal: Kidney International (2021)

We and others have found a high short-term seroconversion rate between 71% and 98% in hemodialysis patients following a complete 2-dose vaccination course with the mRNA-BNT162b2 vaccine (Pfizer–BioNTech).1Carr E.J. Kronbichler A. Graham-Brown M. et al.Review of early immune response to SARS-CoV-2 vaccination among patients with CKD.Kidney Int Rep. 2021; 6: 2292-2304Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar,2Zitt E. Davidovic T. Schimpf J. et al.The safety and immunogenicity of the mRNA-BNT162b2 SARS-CoV-2 vaccine in hemodialysis patients.Front Immunol. 2021; 12: 704773Crossref PubMed Scopus (48) Google Scholar After natural infection, 76% of hemodialysis patients remained seropositive after a median time period of 124 days after infection.3Banham G.D. Godlee A. Faustini S.E. et al.Hemodialysis patients make long-lived antibodies against SARS-CoV-2 that may be associated with reduced reinfection.J Am Soc Nephrol. 2021; 32: 2140-2142Crossref PubMed Scopus (8) Google Scholar However, to our knowledge, there are no serial data available on the maintenance of the vaccine-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) humoral response in hemodialysis patients. Herein, we are reporting on the antibody response over time during a follow-up of 6 months after SARS-CoV-2 vaccination in 41 chronic hemodialysis patients (mean [SD] age, 67.3 [15.5] years; 34.1% females). All patients had been vaccinated twice with the Pfizer–BioNTech mRNA-BNT162b2 coronavirus disease 2019 (COVID-19) vaccine (Comirnaty). Patient characteristics, safety, tolerability, and short-term immunogenicity data have been reported in detail elsewhere.2Zitt E. Davidovic T. Schimpf J. et al.The safety and immunogenicity of the mRNA-BNT162b2 SARS-CoV-2 vaccine in hemodialysis patients.Front Immunol. 2021; 12: 704773Crossref PubMed Scopus (48) Google Scholar We assessed the antibody response again 6 months after vaccination by quantifying the anti–SARS-CoV-2–spike IgG antibody concentration using the LIAISON SARS-CoV-2-TrimericS IgG chemiluminescent immunoassay (Diasorin S.p.A.), which detects IgG antibodies against the trimeric spike glycoprotein, including the receptor-binding domain and the N-terminal domain sites from the S1 subunit. According to the manufacturer, a value of ≥33.8 binding antibody units (BAUs)/ml was considered as evidence of seroconversion. In addition, neutralizing antibodies were assessed via the cPass SARS-CoV-2 Surrogate Virus Neutralization Test assay (GenScript), according to the manufacturer's specifications. The assay was originally described by Tan et al.4Tan C.W. Chia W.N. Qin X. et al.A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction.Nat Biotechnol. 2020; 38: 1073-1078Crossref PubMed Scopus (798) Google Scholar and has received emergency use authorization from the US Food and Drug Administration. The assay provides the percentage neutralization, with <30% classified as negative; 30% to 100% represents a range of low-to-high neutralization ability. A patient flow diagram, further details of study methods and statistical analysis, and patients' characteristics are shown in Supplementary Figure S1, the Supplementary Methods, and Supplementary Table S1. Compared with the seroconversion rate of 97.9% and a median (quartile 1–quartile 3) anti–SARS-CoV-2–spike IgG concentration of 1110 (293.5–1720) BAUs/ml 4 weeks after the second vaccine dose, 6 months later the seroconversion rate decreased to 65.8% with a median anti–SARS-CoV-2–spike IgG concentration of 85.6 (24.5–192.5) BAUs/ml (Figure 1). To further analyze the neutralizing capacity of seropositive patients after 6 months, we additionally assessed neutralizing antibodies. The median (quartile 1–quartile 3) percentage virus neutralization was 40.7% (32.9%–46.7%), and the percentage of patients above the 30% threshold for neutralizing antibody positivity was 56.1% of all patients and 85.2% of seropositive patients. Patients with maintained seroconversion after 6 months had a higher seroconversion rate after the first vaccine dose (63.0% vs. 7.1%; P = 0.001), had a significantly higher absolute anti–SARS-CoV-2–spike IgG concentration after the first (47.6 vs. 12.0 BAUs/ml; P < 0.001) and second (1440 vs. 136.5 BAUs/ml; P < 0.001) vaccine dose, had a higher hepatitis B vaccination seroconversion rate (80% vs. 40%; P = 0.045), and were less often treated with glucocorticoids (7.4% vs. 35.7%; P = 0.035). During the 6 months of follow-up, no patient acquired COVID-19. As a limitation, our study lacks cellular immune response data, including vaccine-induced T-cell response, which was found in 62%–78% of hemodialysis patients 3 to 8 weeks after vaccination with BNT162b2.5Blazquez-Navarro A. Safi L. Meister T.L. et al.Superior cellular and humoral immunity toward SARS-CoV-2 reference and alpha and beta VOC strains in COVID-19 convalescent as compared to the prime boost BNT162b2-vaccinated dialysis patients.Kidney Int. 2021; 100: 698-700Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 6Broseta J.J. Rodriguez-Espinosa D. Rodriguez N. et al.Humoral and cellular responses to mRNA-1273 and BNT162b2 SARS-CoV-2 vaccines administered to hemodialysis patients.Am J Kidney Dis. 2021; 78: 571-581Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar, 7Strengert M. Becker M. Ramos G.M. et al.Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis.EBioMedicine. 2021; 70: 103524Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Further studies are necessary to clarify whether the rapid antibody loss is caused by the impaired immune system in hemodialysis patients or due to the new RNA-based vaccine platform. Nevertheless, a third booster dose after 6 months may be necessary to sustain a protective humoral immunity in this vulnerable patient cohort. Download .pdf (.23 MB) Help with pdf files Supplementary File (PDF) Superior cellular and humoral immunity toward SARS-CoV-2 reference and alpha and beta VOC strains in COVID-19 convalescent as compared to the prime boost BNT162b2-vaccinated dialysis patientsKidney InternationalVol. 100Issue 3PreviewPatients undergoing maintenance dialysis (DP) have a high risk of fatal coronavirus disease 2019 (COVID-19).1 Recent epidemiological data raise apprehension with respect to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) for DP.2,3 Therefore, ensuring cellular and humoral immunity directed to SARS-CoV-2 including VOC isolates is essential for this population. There are no data on vaccine-induced nor on natural SARS-CoV-2 infection–induced long-term immunity and its responsiveness to VOC isolates in DP. 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