Diminishing Immune Responses Against Variants of Concern in Dialysis Patients 4 Months After SARS-CoV-2 mRNA Vaccination

Alex Dulovic; Monika Strengert; Gema Morillas Ramos; Matthias Becker; Johanna Griesbaum; Daniel Junker; Karsten Lürken; Andrea Beigel; Eike Wrenger; Gerhard Lonnemann; Anne Cossmann; Metodi V. Stankov; Alexandra Dopfer-Jablonka; Philipp D. Kaiser; Bjoern Traenkle; Ulrich Rothbauer; Gérard Krause; Nicole Schneiderhan-Marra; Georg M.N. Behrens


Emerging Infectious Diseases. 2022;28(4):743-750. 

In This Article

Abstract and Introduction


Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.


Persistence of vaccination-induced cellular and humoral immune responses is crucial to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or at least provide protection against severe coronavirus disease (COVID-19) that requires hospitalization. As in many other countries, the SARS-CoV-2 vaccination strategy in Germany was based on prioritization by occupation, underlying medical conditions, or advanced age.[1] Although those priority groups have been vaccinated, a debate has emerged as to whether a third booster dose may be necessary to maintain or raise levels of protection within some of these groups. Decisions on whether to recommend a third dose needed to be made within a short timeframe, because SARS-CoV-2 infection case numbers were expected to increase again in the upcoming cold season, as previously observed in late 2020.[2] To date, however, data are lacking regarding the longevity of vaccination responses, and most published studies only provide follow-up data until 3 months after the second dose.[3] Only 2 studies report data on extended time frames of 6 months after a completed 2-dose scheme,[4,5] and, to our knowledge, no studies have considered follow-ups in patients receiving chronic hemodialysis. Data on the actual effect of a third dose are equally scarce and, so far, limited to organ transplant recipients, where a third dose substantially increased antibody responses.[6] In addition, protection offered by first-generation vaccines is reduced for SARS-CoV-2 variants of concern (VOCs),[7] which now account for most infections worldwide,[8] making the decision of whether a third dose is advisable even more critical for those with underlying conditions, immunodeficiencies, or an increased exposure risk (e.g., healthcare workers).

One particular risk group for SARS-CoV-2 infection and severe COVID-19 disease is hemodialysis patients; currently, ≈80,000 persons requiring regular renal replacement therapy in Germany.[9] Their various underlying medical conditions and dialysis therapy often lead to a state of generalized immunosuppression.[10] At the same time, these patients bear a continuous exposure risk because of the regular need for in-center hemodialysis therapy, which prevents them from self-isolating or reducing contacts to avoid infection. We and others have identified impaired cellular and humoral responses towards several viral vaccinations (e.g., SARS-CoV-2, influenza A, or hepatitis B);[10–13] however, there is a lack of longitudinal vaccination response studies against SARS-CoV-2 within this population. To guide future vaccination strategies as to whether additional booster vaccinations for at-risk groups to prevent severe COVID-19 are required, we provide follow-up data for a previously reported cohort of 76 persons receiving hemodialysis and 23 healthcare workers with no underlying conditions[13] for systemic and mucosal B- and T-cell responses 16 weeks after full BNT162b2 vaccination and the neutralizing potency of vaccination-induced antibodies. Because of the emergence of VOCs, and because all currently licensed vaccines are formulated against the original wild-type isolate (B.1), we also examined antibody binding and neutralization toward the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.3) and Delta (B.1.617.2) VOCs.