Significant Fade of Neutralizing Antibodies and Stable Cellular Immunity in 4 Times COVID-19 Vaccinated Noninfected Compared to COVID-19 Convalescent and 3 Times Vaccinated Hemodialysis Patients

Anft, Moritz; Skrzypczyk, Sarah; Frahnert, Michael; Fricke, Lutz; Zapka, Jan; Kühn, Daniel; Koos, Björn; Adamzik, Michael; Pfaender, Stephanie; Stervbo, Ulrik; Westhoff, Timm H.; Babel, Nina

doi:10.1016/j.ekir.2023.01.005

Cited by 3 publications

(3 citation statements)

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“…Similarly, Anft and colleagues recently described a stable cellular immunity with no differences in the production of proinflammatory cytokines (IL-2 and TNF) between four times vaccinated, non-infected HD patients compared to three times vaccinated, infected HD patients. However, a significant fade of neutralizing antibodies after SARS-CoV-2 vaccination in naïve HD patients (25%) compared to COVID-19-recovered HD patients (62.5%) was observed [13]. These results indicate significant differences between the humoral and cellular immune responses and highlight the importance of measuring both arms of the immune response in HD patients.…”

Section: Discussionmentioning

confidence: 86%

“…More recent studies compared the immune response of non-infected naïve HD patients, who received four vaccine doses, with COVID-19-recovered HD patients, who only received three doses of the SARS-CoV-2 mRNA vaccine. The results indicated that, while there were no differences in the production of the proinflammatory cytokines interleukin-2 (IL-2) and tumor necrosis factor (TNF) by T-cells, better humoral immunity was observed in the convalescent-vaccinated compared to vaccinated-only HD patients [13]. These results suggest that the cellular and humoral immune responses provide different information regarding the immunological status of vaccinated HD patients that do not necessarily correlate with each other.…”

Section: Introductionmentioning

confidence: 99%

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Maintenance of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients after 1273-mRNA SARS-CoV-2 Vaccination

et al. 2023

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Continuous evaluation of the coronavirus disease 2019 (COVID-19) vaccine effectiveness in hemodialysis (HD) patients is critical in this immunocompromised patient group with higher mortality rates due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The response towards vaccination in HD patients has been studied weeks after their first and second SARS-CoV-2 vaccination dose administration, but no further studies have been developed in a long-term manner, especially including both the humoral and cellular immune response. Longitudinal studies that monitor the immune response to COVID-19 vaccination in individuals undergoing HD are therefore necessary to prioritize vaccination strategies and minimize the pathogenic effects of SARS-CoV-2 in this high-risk group of patients. We followed up HD patients and healthy volunteers (HV) and monitored their humoral and cellular immune response three months after the second (V2+3M) and after the third vaccination dose (V3+3M), taking into consideration previous COVID-19 infections. Our cellular immunity results show that, while HD patients and HV individuals secrete comparable levels of IFN-γ and IL-2 in ex vivo stimulated whole blood at V2+3M in both naïve and COVID-19-recovered individuals, HD patients secrete higher levels of IFN-γ and IL-2 than HV at V3+3M. This is mainly due to a decay in the cellular immune response in HV individuals after the third dose. In contrast, our humoral immunity results show similar IgG binding antibody units (BAU) between HD patients and HV individuals at V3+3M, independently of their previous infection status. Overall, our results indicate that HD patients maintain strong cellular and humoral immune responses after repeated 1273-mRNA SARS-CoV-2 vaccinations over time. The data also highlights significant differences between cellular and humoral immunity after SARS-CoV-2 vaccination, which emphasizes the importance of monitoring both arms of the immune response in the immunocompromised population.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Maintenance of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients after 1273-mRNA SARS-CoV-2 Vaccination

et al. 2023

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“…An Omicron break-through infection in hemodialysis patients may induce higher Omicron specific antibody titers and less non-responders than vaccination only. A primary variant of concern (VoC) BA.1 or BA.2 infection though, seems to mainly generate variant specific humoral immunity 8, 9 . In older healthy adults, break-through infections seem to generate a more durable humoral immunity than vaccinations alone 10 .…”

Section: Introductionmentioning

confidence: 99%

Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of break-through infections in hemodialysis patients

Platen

Liao

Tellenbach

et al. 2023

Preprint

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Background Individuals on hemodialysis are more vulnerable to SARS-CoV-2 infection than the general population due to end-stage kidney disease-induced immunosuppression. Methods 26 hemodialysis patients experiencing SARS-CoV-2 infection after 3rd vaccination were matched 1:1 to 26 out of 92 SARS-CoV-2 naives by age, sex, dialysis vintage and immunosuppressive drugs receiving a 4th vaccination with an mRNA-based vaccine. A competitive surrogate neutralization assay was used to monitor vaccination success. To determine infection neutralization titers, Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Omicron sub-lineage BA.1, BA.5, and BQ.1.1. 50% inhibitory concentration (IC50, serum dilution factor 1:x) was determined before, four weeks after and 6 months after the 4th vaccination. Results 52 hemodialysis patients received four COVID-19 vaccinations and were followed up for a median of 6.3 months. Patient characteristics did not differ between the matched cohorts. Patients without a SARS-CoV-2 infection had a significant reduction of real virus neutralization capacity for all Omicron sub-lineages after six months (p<0.001 each). Those patients with a virus infection did not experience a reduction of real virus neutralization capacity after six months. Compared to the other Omicron VoC the BQ.1.1 sub-lineage had the lowest virus neutralization capacity. Conclusions SARS-CoV-2-naive hemodialysis patients had significantly decreased virus neutralization capacity six months after the 4th vaccination whereas patients with a SARS-CoV-2 infection had no change in neutralization capacity. This was independent of age, sex, dialysis vintage and immunosuppression. Therefore, in infection-naive hemodialysis patients a fifth COVID-19 vaccination might be reasonable 6 months after the 4th vaccination.

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Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of breakthrough infections in haemodialysis patients

Platen

Liao

Tellenbach

et al. 2023

Clinical Kidney Journal

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Background Individuals on hemodialysis are more vulnerable to SARS-CoV-2 infection than the general population due to end-stage kidney disease-induced immunosuppression. Methods 26 hemodialysis patients experiencing SARS-CoV-2 infection after 3rd vaccination were matched 1:1 to 26 out of 92 SARS-CoV-2 naïves by age, sex, dialysis vintage and immunosuppressive drugs receiving a 4th vaccination with an mRNA-based vaccine. A competitive surrogate neutralization assay was used to monitor vaccination success. To determine infection neutralization titers, Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Omicron sub-lineage BA.1, BA.5, and BQ.1.1. 50% inhibitory concentration (IC50, serum dilution factor 1: x) was determined before, four weeks after and 6 months after the 4th vaccination. Results 52 hemodialysis patients received four COVID-19 vaccinations and were followed up for a median of 6.3 months. Patient characteristics did not differ between the matched cohorts. Patients without a SARS-CoV-2 infection had a significant reduction of real virus neutralization capacity for all Omicron sub-lineages after six months (p < 0.001 each). Those patients with a virus infection did not experience a reduction of real virus neutralization capacity after six months. Compared to the other Omicron VoC the BQ.1.1 sub-lineage had the lowest virus neutralization capacity. Conclusions SARS-CoV-2-naïve hemodialysis patients had significantly decreased virus neutralization capacity six months after the 4th vaccination whereas patients with a SARS-CoV-2 infection had no change in neutralization capacity. This was independent of age, sex, dialysis vintage and immunosuppression. Therefore, in infection-naïve hemodialysis patients a fifth COVID-19 vaccination might be reasonable 6 months after the 4th vaccination.

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Significant Fade of Neutralizing Antibodies and Stable Cellular Immunity in 4 Times COVID-19 Vaccinated Noninfected Compared to COVID-19 Convalescent and 3 Times Vaccinated Hemodialysis Patients

Cited by 3 publications

References 4 publications

Maintenance of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients after 1273-mRNA SARS-CoV-2 Vaccination

Maintenance of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients after 1273-mRNA SARS-CoV-2 Vaccination

Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of break-through infections in hemodialysis patients

Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of breakthrough infections in haemodialysis patients

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