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. 2024 Dec 25;13(1):7.
doi: 10.3390/vaccines13010007.

Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms

Nadezhda Wall  1   2 , Rachel Lamerton  3 , Fiona Ashford  3 , Marisol Perez-Toledo  3 , Aleksandra Jasiulewicz  3 , Gemma D Banham  1   4 , Maddy L Newby  5 , Sian E Faustini  3 , Alex G Richter  2   3 , Haresh Selvaskandan  6   7 , Roseanne E Billany  6   7 , Sherna F Adenwalla  6   7 , Ian R Henderson  8 , Max Crispin  5 , Matthew Graham-Brown  6   7 , Lorraine Harper  1   2 , Adam F Cunningham  3
Affiliations

Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms

Nadezhda Wall et al. Vaccines (Basel). .

Abstract

Background/Objectives: Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Vaccine-induced immunity is typically reduced in HD populations. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen-Spike (S)-glycoprotein-after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Methods: We compared the total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation. Results: After 2 doses of the same vaccine, HD patients had anti-S antibody levels and a complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV (defined by the presence of both complement binding and cross-variant neutralisation activity). Interestingly, an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients without a prior history of SARS-CoV-2 infection. Conclusions: HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population.

Keywords: SARS-CoV-2; antibody; haemodialysis; immune responses; vaccine.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Antigen-specific antibody in sera collected 21–28 days after two doses of SARS-CoV-2 vaccine—comparison between controls and patients requiring HD. Comparisons of anti-S antibody levels between controls (black symbols) and patients requiring HD (orange symbols)—shown in legend. Filled symbols represent individuals with previous SARS-CoV-2 infection. Blue columns denote data from mRNA vaccinees. (A) Data from SARS-CoV-2-naïve individuals only; (B) data from individuals with previous SARS-CoV-2 infection only; (C) all data shown. Threshold level of antibody detection (“seropositivity”) shown as dashed line (0.8 U/mL). Kruskal–Wallis test used to compare groups in panels (A,B), with post hoc Dunn’s multiple comparison p values shown (ns denotes not significant; p > 0.05). The Mann–Whitney U test is used for pre-defined comparisons within groups in panel (C).
Figure 2
Figure 2
Correlation between anti-S antibody levels and the binding of complement components in controls and patients requiring HD. Data shown for all seropositive individuals—(A–D) correspond to C1q, C3b, C4b, and C5b, respectively.
Figure 3
Figure 3
Complement component binding by antigen-specific antibody in sera collected 21–28 days after two doses of SARS-CoV-2 vaccine—comparison between controls and patients requiring HD. Comparisons shown between controls (black symbols) and patients requiring HD (orange symbols) with data grouped by vaccine type and previous SARS-CoV-2 exposure (filled symbols denote previous infection); (A–D) correspond to C1q, C3b, C4b, and C5b, respectively.
Figure 4
Figure 4
Anti-S antibody levels in sera of HD patients 21–28 days after two and three vaccine doses. Anti-S antibody levels in HD patients after two and three vaccine doses—comparisons by first vaccine type (grey—viral vector; blue—mRNA), split by previous SARS-CoV-2 infection (filled symbols denote previous infection)—see legend. Paired statistical comparisons performed between timepoints using Wilcoxon’s signed-rank test (post-dose two vs. post-dose three levels), and Mann–Whitney’s U test was used to compare antibody levels at the same timepoints by previous SARS-CoV-2 exposure (denoted by $).
Figure 5
Figure 5
Antigen-specific antibody functionality in patients requiring HD—comparison between two and three vaccine doses. (A) Diagrammatic representation of antigen-specific antibody functionality after two and three vaccine doses for all HD patients—comparisons by vaccine type. Venn diagrams showing the overlap of neutralisation activity against Delta VoC (Delta nAb +) with the binding of all four complement components tested (C1q-C5b +) to denote antibody with dual function; n and % of total for whom data were available are shown. (B) As above, but for SARS-CoV-2-naïve HD patients only.
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