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. 2025 Jan 12:44:126544.
doi: 10.1016/j.vaccine.2024.126544. Epub 2024 Nov 29.

COVID-19 vaccine responses are influenced by distinct risk factors in naive and SARS-CoV-2 experienced hemodialysis recipients

Nicolas Gemander  1 , Delphine Kemlin  2 , Stéphanie Depickère  3 , Natasha S Kelkar  4 , Shilpee Sharma  5 , Pieter Pannus  5 , Alexandra Waegemans  5 , Véronique Olislagers  5 , Daphnée Georges  6 , Emilie Dhondt  7 , Margarida Braga  7 , Leo Heyndrickx  7 , Johan Michiels  7 , Anaïs Thiriard  5 , Anne Lemy  8 , Thomas Baudoux  9 , Marylène Vandevenne  10 , Maria E Goossens  3 , André Matagne  10 , Isabelle Desombere  11 , Kevin K Ariën  12 , Margaret E Ackerman  13 , Alain Le Moine  2 , Arnaud Marchant  5
Affiliations

COVID-19 vaccine responses are influenced by distinct risk factors in naive and SARS-CoV-2 experienced hemodialysis recipients

Nicolas Gemander et al. Vaccine. .

Abstract

Background: Clinical risk factors of deficient immune responses to COVID-19 mRNA vaccination in SARS-CoV-2 naive hemodialysis recipients (HDR) have already been identified. Clinical factors influencing hybrid immunity induced by SARS-CoV-2 infection and vaccination in HDR have not been reported.

Methods: A comprehensive analysis of antibody (Ab) and T cell responses to two doses of BNT162b2 mRNA vaccination was performed in 103 HDR, including 75 SARS-CoV-2 naive and 28 experienced patients, and in 106 healthy controls (HC) not undergoing HD, including 40 SARS-CoV-2 naive and 66 experienced subjects. Clinical risk factors associated with lower humoral and cellular immunity were analyzed in SARS-CoV-2 naive and experienced HDR by univariate and multivariate analyses.

Results: Naive HDR had lower neutralizing and non-neutralizing antibody responses to vaccination than naive HC; lower vaccine responses were correlated with previous transplantation, immunosuppressive treatment, corticosteroid treatment, hypoalbuminemia, older age, hypertension, and negative response to hepatitis B vaccination. In contrast, vaccine responses of SARS-CoV-2 experienced HDR were similar to those of HC and were correlated with time between infection and vaccination and with previous transplantation, but not with the other risk factors associated with lower vaccine responses in naive HDR.

Conclusion: COVID-19 vaccine responses are influenced by distinct risk factors in SARS-CoV-2 naive and experienced HDR. These observations have important implications for the understanding of vaccine-induced immunity and for the management of this vulnerable patient population.

Keywords: COVID-19; Hemodialysis; Hybrid immunity; Systems immunology; mRNA vaccination.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicolas Gemander reports financial support was provided by Sciensano. Margaret Ackerman reports financial support was provided by US NIAID (grants R56AI165448 and P01AI162242). Margaret Ackerman reports financial support was provided by NIH NIGMS. Margaret Ackerman reports financial support was provided by Bill and Melinda Gates Foundation. Margaret Ackerman reports financial support was provided by SD Ireland Foundation. Margaret Ackerman reports equipment, drugs, or supplies was provided by Johns Hopkins Universities. Margaret Ackerman reports article publishing charges was provided by Elsevier. Margaret Ackerman reports financial support was provided by Seromyx systems. Margaret Ackerman reports financial support was provided by Keystone Conferences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.. Binding IgG, RBD IgG avidity and neutralizing antibody responses to SARS-CoV-2 mRNA vaccination in naive and experienced HDR and HC.
Serum levels of SARS-CoV-2 receptor binding domain (RBD) specific binding IgG (BAU: binding antibody units), RBD specific IgG avidity (koff: dissociation rate constant) and titers of neutralizing antibodies (NT50: 50% neutralization titer) were measured before vaccination (D0) and 1 month after 2 doses of mRNA vaccine (D49) in naive hemodialysis recipients (N-HDR, light green), experienced (E-)HDR (dark green), naive healthy controls (N-HC, light blue) and experienced (E-)HC (dark blue). Bars indicate median values. Horizontal dashed lines indicate a technical negative signal (blank). Dunn’s test results using Bonferroni correction are shown as followed: for within HC or HDR comparisons, ns: not significant; *:p<0.05; **:p<0.01; ***:p<0.001; for comparisons between HC and HDR, ns: not significant; #:p<0.05; ##:p<0.01; ###:p<0.001.
Figure 2.
Figure 2.. IgG Subclasses and IgA responses to SARS-CoV-2 mRNA vaccination in naive and experienced HDR and HC.
Serum levels of SARS-CoV-2 Receptor Binding Domain (RBD) specific, spike S1 subunit specific, and spike S2 subunit specific IgG1, IgG2, IgG3, IgG4 and IgA were measured before vaccination (D0, panel A) and 1 month after vaccination (D49, panel B) in naive hemodialysis recipients (N-HDR, light green), experienced (E-)HDR (dark green), naive healthy controls (N-HC, light blue) and experienced (E-)HC (dark blue). MFI: median fluorescent intensity. Bars indicate median values. Horizontal dashed lines indicate a technical negative signal (blank). Dunn’s test results using Bonferroni correction are shown as followed: for within HC or HDR comparisons, ns: not significant; *:p<0.05; **:p<0.01; ***:p<0.001; for comparisons between HC and HDR, ns: not significant; #:p<0.05; ##:p<0.01; ###:p<0.001.
Figure 3.
Figure 3.. Fcγ receptors binding antibody responses to SARS-CoV-2 mRNA vaccination in naive and experienced HDR and HC.
Serum levels of SARS-CoV-2 Receptor Binding Domain (RBD) specific, spike S1 subunit specific, and spike S2 subunit specific antibodies binding the Fcγ receptors FcγRIIa and FcγRIIIa were measured before vaccination (D0, panel A) and 1 month after vaccination (D49, panel B) in naive hemodialysis recipients (N-HDR, light green), experienced (E-)HDR (dark green), naive healthy controls (N-HC, light blue) and experienced (E-)HC (dark blue). MFI: median fluorescent intensity. Bars indicate median values. Horizontal dashed lines indicate a technical negative signal (blank). Dunn’s test results using Bonferroni correction are shown as followed: for within HC or HDR comparisons, ns: not significant; *:p<0.05; **:p<0.01; ***:p<0.001; for comparisons between HC and HDR, ns: not significant; #:p<0.05; ##:p<0.01; ###:p<0.001.
Figure 4.
Figure 4.. IgG-dependent complement deposition and phagocytosis responses to SARS-CoV-2 mRNA vaccination in naive and experienced HDR and HC.
Serum levels of SARS-CoV-2 Receptor Binding Domain (RBD) specific, spike S1 subunit specific, and spike S2 subunit specific IgG promoting complement deposition (ADCD) and cellular phagocytosis (ADCP) were measured before vaccination (D0, panel A) and 1 month after vaccination (D49, panel B) in naive hemodialysis recipients (N-HDR, light green), experienced (E-)HDR (dark green), naive healthy controls (N-HC, light blue) and experienced (E-)HC (dark blue). Levels of ADCD are expressed as MFI: median fluorescent intensity. Levels of ADCP are expressed as phagocytic score (see methods). Bars indicate median values. Horizontal dashed lines indicate a technical negative signal (blank). Dunn’s test results using Bonferroni correction are shown as followed: for within HC or HDR comparisons, ns: not significant; *:p<0.05; **:p<0.01; ***:p<0.001; for comparisons between HC and HDR, ns: not significant; #:p<0.05; ##:p<0.01; ###:p<0.001.
Figure 5.
Figure 5.. CD4 and CD8 T cell responses to SARS-CoV-2 mRNA vaccination in naive and experienced HDR and HC.
Percentage of SARS-CoV-2 spike S1 subunit and spike S2 subunit specific CD4 T cells expressing CD154, IFNγ and IL2, and of CD8 T cells expressing IFNγ and IL2 were measured in peripheral blood before vaccination (D0, panel A) and 1 month after vaccination (D49, panel B) in naive hemodialysis recipients (N-HDR, light green), experienced (E-)HDR (dark green), naive healthy controls (N-HC, light blue) and experienced (E-)HC (dark blue). Bars indicate median values. Dunn’s test results using Bonferroni correction are shown as followed: for within HC or HDR comparisons, ns: not significant; *:p<0.05; **:p<0.01; ***:p<0.001; for comparisons between HC and HDR, ns: not significant; #:p<0.05; ##:p<0.01; ###:p<0.001.
Figure 6.
Figure 6.. Principal component analysis of immune responses to SARS-CoV-2 mRNA vaccination in naive and experienced HDR and HC.
A. Scatter plot of principal component analysis (PCA) including all immune response parameters except IgG2, IgG4 and IgA measured 1 month after vaccination (D49) in naive hemodialysis recipients (N-HDR, light green), experienced (E-)HDR (dark green), naive healthy controls (N-HC, light blue) and experienced (E-)HC (dark blue). Colored ellipses (size determined by a 0.95 probability level) show the observances grouped by the marked class. B. Comparison of PC1 and PC2 values between groups by Dunn’s test results using Bonferroni correction with p<0.05. *:p<0.05; **:p<0.01; ***:p<0.001. C. Relative weighting of individual immune response parameters in PC1 and PC2. PC: principal component.
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