Inferior cellular and humoral immunity against Omicron and Delta variants of concern compared with SARS-CoV-2 wild type in hemodialysis patients immunized with 4 SARS-CoV-2 vaccine doses

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With the dominance of the most recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern Omicron (B.1.1.529), the question arises, what is the reason for its high contagiousness in coronavirus disease 2019 (COVID-19)–vaccinated dialysis patients compared with the previous SARS-CoV-2 variants Delta and wild type? The objective of this study was, therefore, to analyze humoral and cellular immunity directed against the Omicron variant of concern compared with the wild-type or Delta variant of concern in hemodialysis patients (n = 42; Supplementary Table S1) immunized with 4 doses of mRNA COVID-19 vaccine. Titers of neutralizing antibodies (NAbs) against wild type, Delta, and Omicron were estimated by SARS-CoV-2 spike-protein (S-protein) pseudovirus assays. T-cell immunity reactive against wild-type, Delta-derived, and Omicron-derived S-protein was analyzed by multiparameter flow cytometry (Supplementary Figure S1). The analyses were performed 8 to 9 weeks following the fourth doses. The hemodialysis patients had a clear seroconversion after 4 doses of SARS-CoV-2 vaccination, with a significantly higher titer of NAb against wild type compared with Delta or Omicron S-protein (median [interquartile range]-50% Neutralizing Dose [ND50] = 2117 [663–2560], 759 [276–2560], and 439 [160–1180], respectively). Interestingly, the NAb titer against Delta was significantly higher compared with Omicron-specific NAb (Figure 1a). Although the number of patients with a detectable S-protein–reactive CD4 T-cell response was nearly identical (40–41 of 42 patients; Supplementary Table S2), the magnitude of response was significantly lower against Omicron- and Delta-derived S-protein compared with wild type (Figure 1b). In contrast, significantly fewer patients showed a detectable S-protein–reactive CD8 T-cell response against Omicron but not Delta compared with wild type (P = 0.0304, Fisher exact test; Supplementary Table S2), although the magnitude of response was not different between all 3 SARS-CoV-2 variants (Figure 1c). With regard to the functionality, the frequency of Omicron and Delta S-protein–reactive CD4+ T cells producing T helper cell 1 cytokines interferon-γ and tumor necrosis factor was significantly lower compared with wild-type S-protein–reactive CD4+ T cells (Figure 1d and f). In line with the results from the general populations,1GeurtsvanKessel C.H. Geers D. Schmitz K.S. et al.Divergent SARS-CoV-2 Omicron–reactive T and B cell responses in COVID-19 vaccine recipients.Sci Immunol. 2022; 7: 1-15Crossref Scopus (115) Google Scholar,2Ariën K.K. Heydrickx L. Michiels J. et al.Three doses of BNT162b2 vaccine confer neutralising antibody capacity against the SARS-CoV-2 Omicron variant.NPJ Vaccines. 2022; 7: 4-6Crossref PubMed Scopus (15) Google Scholar hemodialysis patients show a clearly decreased humoral and cellular immune response against Omicron compared with SARS-CoV-2 wild type after 4 doses of vaccination. Of interest, Omicron-specific NAb titer was significantly lower compared with Delta-specific NAb, explaining the more efficient evasion of Omicron from neutralizing antibodies3Hoffmann M. Krüger N. Schulz S. et al.The Omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic.Cell. 2022; 185: 447-456Abstract Full Text Full Text PDF PubMed Scopus (319) Google Scholar and its efficient spread in vaccinated individuals.4Arora P. Zhang L. Rocha C. et al.Comparable neutralisation evasion of SARS-CoV-2 omicron subvariants BA.1, BA.2, and BA.3.Lancet Infect Dis. 2022; 22: 766-767Abstract Full Text Full Text PDF Scopus (34) Google Scholar Because the humoral immune response of dialysis patients strongly benefits from a fourth compared with a third vaccination,5Cinkilic O. Anft M. Blazquez-Navarro A. et al.Inferior humoral and sustained cellular immunity against wild-type and omicron variant of concern in hemodialysis patients immunized with 3 SARS-CoV-2 vaccine doses compared with 4 doses.Kidney Int. 2022; 101: 1287-1289Abstract Full Text Full Text PDF Scopus (6) Google Scholar an adjustment of the vaccination procedure should be recommended. The data will be available on request. We feel deep gratitude to the patients who donated their blood samples for this project. We would like to acknowledge the excellent assistance of dialysis staff of Dialyse-Bochum as well as the expertise and technical assistance of immune diagnostic laboratory (Sviatlana Kaliszczyk, Patrizia Wehler, Sarah Skrzypczyk, Eva Kohut, Julia Kurek, and Jan Zapka) of Center for Translational Medicine at Marien Hospital Herne. This work was supported by grants of Mercator Foundation, COVIDDataNet.NRW, and the EpiCov project from Arbeitsgemeinschaft industrieller Forschungsvereinigungen (AiF)/Zentrale Innovationsprogramm Mittelstand (ZIM). Download .pdf (.49 MB) Help with pdf files Supplementary File (PDF)