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. 2022 Aug 16;10(8):1328.
doi: 10.3390/vaccines10081328.

Improved SARS-CoV-2 Neutralization of Delta and Omicron BA.1 Variants of Concern after Fourth Vaccination in Hemodialysis Patients

Cho-Chin Cheng  1 , Louise Platen  2 , Catharina Christa  1 , Myriam Tellenbach  2 , Verena Kappler  2 , Romina Bester  1 , Bo-Hung Liao  1 , Christopher Holzmann-Littig  2   3 , Maia Werz  2 , Emely Schönhals  2 , Eva Platen  4 , Peter Eggerer  5 , Laëtitia Tréguer  6 , Claudius Küchle  2 , Christoph Schmaderer  2 , Uwe Heemann  2 , Lutz Renders  2   7 , Ulrike Protzer  1   7   8 , Matthias Christoph Braunisch  2
Affiliations

Improved SARS-CoV-2 Neutralization of Delta and Omicron BA.1 Variants of Concern after Fourth Vaccination in Hemodialysis Patients

Cho-Chin Cheng et al. Vaccines (Basel). .

Abstract

Hemodialysis patients are exposed to a markedly increased risk when infected with SARS-CoV-2. To date, it is unclear if hemodialysis patients benefit from four vaccinations. A total of 142 hemodialysis patients received four COVID-19 vaccinations until March 2022. RDB binding antibody titers were determined in a competitive surrogate neutralization assay. Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Delta (B.1.617.2), or Omicron (B.1.1.529, sub-lineage BA.1) to determine serum infection neutralization capacity. Four weeks after the fourth vaccination, serum infection neutralization capacity significantly increased from a 50% inhibitory concentration (IC50, serum dilution factor 1:x) of 247.0 (46.3−1560.8) to 2560.0 (1174.0−2560.0) for the Delta VoC, and from 37.5 (20.0−198.8) to 668.5 (182.2−2560.0) for the Omicron VoC (each p < 0.001) compared to four months after the third vaccination. A significant increase in the neutralization capacity was even observed for patients with high antibody titers after three vaccinations (p < 0.001). Ten patients with SARS-CoV-2 breakthrough infection after the first blood sampling had by trend lower prior neutralization capacity for Omicron (p = 0.051). Our findings suggest that hemodialysis patients benefit from a fourth vaccination in particular in the light of the highly infectious SARS-CoV-2 Omicron-variants. A routinely applied four-time vaccination seems to broaden immunity against variants and would be recommended in hemodialysis patients.

Keywords: COVID-19 vaccination; SARS-CoV-2; hemodialysis; in-vitro viral neutralization.

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Conflict of interest statement

The authors declare no conflict of interest. UP is receiving grants from Hoehnle AG, SCG Cell Therapy and VirBio and personal fees from Abbott, Abbvie, Arbutus, Gilead, GSK, J&amp;J, Roche, Sanofi, Sobi and Vaccitech. UP is co-founder and share-holder of SCG Cell Therapy.

Figures

Figure 1
Figure 1
Flow chart of the COVIIMP study (A). Study design and observed SARS-CoV-2 infection cases (B). Abbreviations: vac., vaccination.
Figure 2
Figure 2
Changes in SARS-CoV-2 infection neutralization capacity before and after the fourth COVID-19 vaccination in hemodialysis patients. Real virus neutralization assay was performed using (A) the SARS-CoV-2 Delta (B.1.617.2) and (B) the Omicron (B.1.1.529, sub-lineage BA.1) variant of concern upon serial dilution of hemodialysis patient sera before and after the fourth vaccination. Inhibitory concentration (IC50) dilution values are given. (C) Change of spike-specific IgG neutralizing antibody (NAb) titers given in AU/mL in a surrogate neutralization assay. Dots indicate the measurement of an individual patient with lines connecting individual patient values before and after the fourth vaccination. Boxes indicate median and interquartile ranges. Statistical analysis was performed using paired-samples Wilcoxon test, p values indicate statistical significance between groups.
Figure 3
Figure 3
Percentage of responders before and after the fourth vaccination. A responder was defined by a Delta or Omicron BA.1 IC50 virus infection neutralization of >1:20 as well as neutralizing antibodies (NAb) ≥10 AU/mL. Green and red indicate the percentages classified as responder and non-responder, respectively. Statistical analysis was done using the McNemar test for paired samples.
Figure 4
Figure 4
Influence of immunosuppressive medication, SARS-CoV-2 breakthrough infection, and hepatitis B response status on COVID-19 vaccine responses. Serum real-virus neutralization capacity for Delta (left column) and Omicron BA.1 (right column) was analyzed after the fourth vaccination in subgroups. Comparison of immunosuppressive drug treatment (A,B), the prevalence of SARS-CoV-2 infection before the second blood sampling (C,D), and hepatitis B vaccination non-response (E,F) on serum neutralization capacity. Statistical analysis was performed using the Mann-Whitney-U test, p values indicate statistical significance between groups.
Figure 5
Figure 5
Serum neutralization capacity for Omicron BA.1 variant of concern before the fourth vaccination stratified by patients with SARS-CoV-2 breakthrough infections between the first and the second blood sampling. Statistical analysis was performed using the Mann-Whitney-U test, p value indicates statistical significance between groups. The y-axis is interrupted between 500 and 2500 for better visibility.
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