Humoral response to a third injection of BNT162b2 vaccine in patients on maintenance haemodialysis

Abstract

Background: Humoral response against sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after two doses of BNT162b2 (Pfizer-BioNTech) has been proven to be less intense in maintenance dialysis patients as compared with healthy subjects, leading the French authorities to recommend a third injection in this population. Here we investigated the response to the third injection in two cohorts of haemodialysis (HD) patients.

Methods: Data from two prospective observational cohorts were collected. In the first ('systematic') cohort, patients from two HD centres (n = 66) received a third injection of BNT162b2, regardless of the response after two injections. In the second ('conditional') cohort, the injection was only prescribed to patients (n = 34) with no or low response to the previous two doses. In both cohorts, the third dose was injected 1-2 months after the second dose. Serology was performed after the second and third doses to assess anti-Spike immunoglobulin G (S IgG) antibody titre.

Results: In the systematic cohort, anti-S IgG was found in 83.3 and 92.4% of patients after the second and third doses of BNT162b2, respectively. In this cohort, 6/11 (54.5%) and 20/21 (95.2%) patients switched from non-responder to low responder and from low responder to high responder, respectively. In low and high responders to two doses, 50/55 (90.9%) at least doubled their anti-S IgG titre. Similar trends were observed in the conditional cohort.

Conclusions: In maintenance HD patients, humoral response against SARS-CoV-2 was boosted after a third dose of BNT162b2, allowing seroconversion in more than half of non-responders. These data may support an intensified vaccination protocol with a third dose of BNT162b2 in dialysis patients.

Keywords: BNT162b2 vaccine; COVID-19; SARS-Cov-2; haemodialysis; immunogenicity.

Graphical Abstract

FIGURE 1:

Study flowchart. The study was composed of two prospective observational cohorts. In the systematic cohort (left panel), all patients from two dialysis centres received a third dose of BNT162b2 regardless of the anti-S IgG titre measured after the second dose. In the conditional cohort (right panel), the third dose of BNT162b2 was given to patients who did not develop or developed a low anti-S IgG titre after the second dose.

FIGURE 2:

Anti-S IgG titre after the second and third BNT162b2 doses in the (A) systematic and (B) conditional cohorts. Each patient is represented by a square. The red dashed line represents the cut-off level for high response to vaccine (anti-S IgG antibody >1000 AU/mL in the systematic cohort and >80 U/mL in the conditional cohort). Comparisons were made using the Mann–Whitney U test. Logarithmic scale.

FIGURE 3:

Percentage of patients according to response status after the second and third dose of BNT162b2 in the (A) systematic and (B) conditional cohorts.

FIGURE 4:

Kinetics of anti-S IgG titre between the second and third dose of BNT162b2 in the systematic cohort in (A) non-responders, (B) low reponders and (C) high responders. Each patient is represented by two squares with a connecting line. The red dashed line represents the cut-off value for test positivity. Comparisons were made using the Wilcoxon matched pairs ranked test. Logarithmic scale.

FIGURE 5:

Anti-S IgG after the second and third dose of BNT162b2 in the systematic cohort. (A) The increase in anti-S IgG titre after the third dose. Logarithmic scale. (B) Correlation between the anti-S IgG titres measured after the second and third dose. Linear scale.