Immunogenicity of Bivalent Omicron BA.4/5–Adapted Vaccine in Hemodialysis Patients

To the Editor:

Owing to immune system alterations, patients with kidney failure are known to be at high risk for infections, including severe COVID-19. Vaccination against infections with effective vaccines is of paramount importance in this vulnerable population.¹ Immune escape of SARS-CoV-2 and antibody fade led to the loss of protection against Omicron variant of concern during recent months. Booster vaccination is an efficient way to address the waning protection of vaccines,² and a new bivalent (Original and Omicron BA.4/5) adapted vaccine demonstrated robust neutralizing antibody response in phase 2/3 clinical trial.³ Immunogenicity of this new bivalent COVID-19 vaccine in hemodialysis patients has not yet been evaluated. The aim of the current study was to evaluate humoral and cellular immune response to wild-type (WT) and Omicron BA.4/5 before and 4 weeks after vaccinating hemodialysis patients with the bivalent COVID-19 mRNA (Pfizer/BioNtech).

A total of 35 hemodialysis patients were included in the study (Supplementary Table S1, Supplementary Figure S1). Although the incidence of humoral response against the WT as defined by positive titers of neutralizing antibodies in pseudovirus assay was very high already before the vaccination, we observed a significant increase in the incidence of positive neutralizing immunity against BA.4/5 with neutralization in 34 of 35 patients (Figure 1a). Titers of neutralizing antibodies increased significantly following vaccination against WT and BA.4/5, and antibodies against BA.4/5 demonstrated a significantly higher increase (Figure 1b). Of interest, high titers of WT neutralizing antibodies ensured neutralizing capacity against BA.4/5 already before bivalent vaccination, as demonstrated by significantly higher titers and number of patients with positive BA.4/5 neutralizing response in patients with high antibody titers against WT and by the correlation between WT and BA.4/5 neutralizing antibody titers (Figure 1c and d). Similar to humoral response, an increase in the incidence of detectable SARS-CoV-2 CD4⁺ and CD8⁺ T cells (Figure 1e and f, Supplementary Figure S2) as well as their frequencies (Figure 1g, Supplementary Figure S3) against WT and BA.4/5 was demonstrated. An increased cellular functionality could be demonstrated by increased frequencies of granzyme B, interferon gamma, interleukin-2, and tumor necrosis factor producing CD4⁺ and CD8⁺ T cells against BA.4/5 (Figure 1h and i) and WT (Supplementary Figure S4). The vaccine was well tolerated with no severe side effects.

Figure 1.

Humoral and cellular immune response of 35 HD patients prior (pre-BV, blue) and post (post-BV, red) BV with SARS-CoV-2 BA.4/5 vaccine. (a) Percentage of patients with a humoral immune response against SARS-CoV-2 WT and Omicron BA.4/5. A humoral immune response was defined as NAb titer [ND50] > 20. (b) Isolated serum from all HD patients was analyzed for titers [ND50] of NAbs against WT or BA.4/5 VOC before or after bivalent vaccination. (c) Titers [ND50] of NAbs against SARS-CoV-2 WT in patients with a humoral immune response against Omicron BA.4/5 (NAb titer [ND50] > 20) before bivalent vaccination. (d) Pearson correlation of NAbs against WT compared with BA.4/5 before bivalent vaccination. (e,f) Percentage of patients with a CD4 or CD8 T-cell immune response against SARS-CoV-2 WT and Omicron BA.4/5. T-cell immune response was defined as CD8⁺CD137⁺ or CD4⁺CD154⁺CD137⁺ T cells > 0.001% after the nonspecific background was subtracted. (g) Isolated peripheral blood mononuclear cells from HD patients were stimulated for 16 hours with 1 μg/ml SARS-CoV-2 BA.4/5 overlapping peptide pools. SARS-CoV-2–reactive T-helper cells were identified as Life/Dead-Marker-CD3⁺CD4⁺CD154⁺CD137⁺, and SARS-CoV-2–reactive cytotoxic T cells were identified as Life/Dead-Marker-CD3⁺CD8⁺CD137⁺. Percentage of SARS-CoV-2–reactive CD4 (h) or CD8 (i) T cells expressing granzyme B, IFN gamma, IL-2, or TNF. Differences between prior- and postbivalent BA.4/5 vaccination were analyzed by Mann-Whitney U test, and a P value below 0.05 is considered significant. BV, bivalent vaccination; HD, hemodialysis; IFN, interferon; IL, interleukin; NAb, neutralizing antibody; ND50, 50% neutralizing dose; TNF, tumor necrosis factor; WT, wild-type.

In conclusion, the demonstrated immunogenicity of the novel bivalent COVID-19 vaccine in hemodialysis patients suggests its strong protection against novel Omicron variants of concern and should be strongly recommended for this vulnerable population.

Supplementary Materials

Supplementary Methods.

Figure S1. Schematic illustration of the course of vaccination and analysis.

Figure S2. Gating strategy.

Figure S3. Identification of SARS-CoV-2 wild-type–specific T cells.

Figure S4. Identification of cytokine expressing SARS-CoV-2 wild-type–specific T cells.

Table S1. Study population.