Blunted humoral immune response to the fourth dose of BNT162b2 COVID-19 vaccine in patients undergoing hemodialysis

Abstract

Background: We aimed to investigate the impact of a fourth dose of BNT162b2 vaccine (Comirnaty®, Pfizer-BioNTech) on anti-SARS-CoV-2 (anti-S IgG) antibody titers in patients receiving hemodialysis (HD) and healthcare workers (HCWs).

Methods: A multi-institutional retrospective study at five dialysis clinics in Japan was conducted using 238 HD patients and 58 HCW controls who received four doses of the BNT162b2 mRNA vaccine. Anti-S IgG titers were measured at 1, 3, and 6 months after the second dose, at 1 and 5/6 months after the third dose, and at 1 month after the fourth dose of vaccine.

Results: The log anti-S IgG titers of the HD patients after the second vaccination were significantly lower than those of the control group, but equalized 1 month after the third vaccination: 9.94 (95% CI 9.82-10.10) vs. 9.81 (95% CI 9.66-9.96), (P = 0.32). In both groups, the fold-increase in anti-S IgG titers was significantly lower after the fourth dose than after the third dose of vaccine. In addition, there was a strong negative correlation between antibody titers 1 month after the fourth vaccination and antibody titers immediately before the vaccination. In both groups, the waning rate of anti-S IgG titers from the post-vaccination peak level after the third vaccine dose was significantly slower than that after the second dose.

Conclusions: These findings suggest that the humoral immune response was blunted after the fourth dose of the conventional BNT162b2 vaccine. However, multiple vaccinations could extend the window of humoral immune protection.

Keywords: Antibody; BNT162b2; Hemodialysis; SARS-CoV-2; Spike protein; Vaccine.

Fig. 1

Changes in the anti-S IgG titers. Changes in the natural logarithmic form of the anti-S IgG titers are shown. Points and error bars show mean ± 95% confidential interval of log-transformed anti-S IgG titers in the HD group (triangles) and in the HCW group (circles). The vaccination time points are also shown below the x-axis for the HD group (arrows with triangular tip) and the HCW group (arrows with rounded tip). HD group vs. HCW group comparisons were performed using Welch’s t-test. ***P < 0.001. HCW healthcare worker, HD hemodialysis

Fig. 2

Fold increase in the anti-S IgG titer after the fourth vaccine dose. A Comparison of humoral immune responses between the third and the fourth vaccine doses. The box and whisker chart shows a fold increase in the anti-S IgG titer after the third and fourth doses in the HD and HCW groups. The whisker on the upper side is drawn to 1.5 times the interquartile range (IQR) of the third quartile; the whisker on the lower side is the minimum. The outliers are indicated by individual dots. The Wilcoxon signed-rank test was used to compare fold changes in anti-S IgG titer after the third vaccine dose with that after the fourth dose. *P < 0.05, **P < 0.01, ***P < 0.001. HD hemodialysis, HCW healthcare worker. B Correlation between fold increase in the anti-S IgG titer after the fourth vaccine dose and the anti-S IgG titer immediately before the fourth dose. The scatterplots show the relationship between the fold increase in anti-S IgG after the fourth dose and the log-transformed anti-S IgG titer immediately before the fourth dose in both the HD and HCW groups. The strength of the relationship was assessed by Spearman’s rank correlation coefficient.$\rho$, correlation coefficient. ***P < 0.001. HD hemodialysis, HCW healthcare worker

Fig. 3

Transitions between peak anti-S IgG titers at 1 month after the second, third, and fourth vaccinations. Points show log-transformed anti-S IgG titers in the HD group (triangles) and in the HCW group (circles). Data points obtained from the same participant are connected by straight lines. HD hemodialysis, HCW healthcare worker