Neutralizing antibody response against variants of concern after vaccination of dialysis patients with BNT162b2

To the editor:

We and others showed high seroconversion rates after BNT162b2 mRNA vaccination in patients on hemodialysis, but still significantly lower rates as compared to those of healthy controls.1, 2, 3 Variants of concern (VOCs) such as B.1.351 (beta variant) or B.1.617.2 (delta variant) partially escape from neutralizing antibodies (NAbs) and will probably replace wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or the B.1.1.7 (alpha) variant with increasing immunity in the population, induced by natural infection or vaccination. Wall et al. ⁴ recently revealed a 4- to 6-fold reduction in vaccine-induced peak NAbs against VOCs B.1.351 and B.1.617.2 in healthy controls compared with wild-type SARS-CoV-2 and the B.1.1.7 variant. Immune-compromised populations such as dialysis patients mounting lower NAbs might become most sensitive to VOCs.

We investigated the neutralization of variants B.1.1.7 and B.1.351 in SARS-CoV-2 infection–based experiments on VeroE6 cells using sera taken 3 weeks after the second BNT162b2 dose in a dual-center cohort of 30 patients receiving maintenance hemodialysis and 18 healthy controls. Only individuals with seroconversion, defined as detectable anti-spike(S)1 antibodies and >30% inhibition in a surrogate neutralization test, were included.

Seropositivity rate was 24 of 30 (80%) in dialysis patients having a median age of 78 years (interquartile range [IQR]: 69–88 years; Supplementary Table S1). The median S1-IgG index was 6 (IQR: 1–19) and the median inhibition in the surrogate neutralization test was 55% (IQR: 32%–78%; Figure 1 a and b). All 24 seropositive dialysis patients had NAbs against the B.1.1.7 strain with a median ID₅₀ (i.e., serum dilution that inhibits 50% of the infectivity) of 160 (IQR: 50–320; Figure 1c). However, NAbs against the VOC B.1.351 were only detected in 15 of 24 patients (63%). With a median of 15 (IQR: 0–20), the ID₅₀ was significantly lower as compared to that of the B.1.1.7 strain (P < 0.001; Figure 1c). In contrast, all 18 healthy controls showed neutralizing activity against both B.1.1.7 and B.1.351, with significantly higher ID₅₀ values compared with those of dialysis patients, respectively (Figure 1c). The S1-IgG index of dialysis patients correlated well with the ID₅₀ of both B.1.1.7 and B.1.351 (Figure 1d). Of note, even dialysis patients with low anti-S1–IgG antibody levels had detectable neutralization against B.1.1.7, whereas this was not the case for B.1.351 in the same patients (Figure 1d).

Figure 1.

Neutralization of B.1.1.7 and B.1.351 after BNT162b2 mRNA vaccination of dialysis patients and healthy controls. (a) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody titers in dialysis patients and healthy controls were measured 3 weeks after the second BNT162b2 mRNA dose and are represented logarithmically as an anti-S1–IgG index. The dashed black line represents the cutoff for detection. A semiquantitative index of <1 was classified as negative, and a value of ≥1 as positive. (b) Antibody-mediated inhibition of the SARS-CoV-2 receptor-binding domain–angiotensin-converting enzyme 2 interaction in dialysis patients and healthy controls. Values were normalized to a negative control (see Supplementary Methods) and are given as percentages. A cutoff of <30% binding inhibition (dashed black line) indicates the limit of detection of this test. (c) Titers of neutralizing antibodies against the B.1.1.7 and B.1.351 variants were determined in a SARS-CoV-2 infection assay using VeroE6 target cells and serial 2-fold serum dilutions. Shown are only values obtained with sera from dialysis patients and healthy controls who exceeded the cutoffs of (a) and (b), respectively. Neutralization titers refer to the serum dilution that inhibits 50% of the infectivity (ID₅₀). Neutralization of different strains was assessed using the nonparametric t test with Well’s correction or the Mann-Whitney U test. (d) The correlation between the anti-S1–IgG index and the neutralization of the respective SARS-CoV-2 strain was examined in dialysis patients using Spearman’s correlation analysis. ∗∗∗P < 0.001. sVNT, surrogate neutralization test; VOC, variant of concern.

Overall, this study suggests that a large proportion of dialysis patients may not be adequately protected against VOCs with vaccination regimens currently applied in the healthy general population. Even if SARS-CoV-2–specific antibodies are detectable by commercially available tests, neutralization of VOCs may be insufficient to protect against infection. Further immunization strategies of dialysis patients seem to be urgently indicated, especially in regions with rapidly increasing VOC prevalence.

Data Availability Statement

The data underlying this article will be shared on reasonable request to the corresponding author.