Comparative analysis of humoral responses to BNT162b2 vaccine among patients with hematologic disorders and organ transplant recipients

Abstract

Vaccination against SARS-COV-2 is considered the most promising approach to curbing the pandemic. Patients with an immunocompromised state, such as those with hematological malignancies and organ transplantation recipients, are considered more susceptible to infection, but these at-risk patients were underrepresented in early clinical trials for vaccination. Although a growing body of studies suggests that the humoral response to COVID-19 vaccination in each of these at-risk groups of patients may be suboptimal in comparison to healthy controls, a clinical and strategic information for the further comparative analysis among these groups is not fully described. The humoral responses after two doses of BNT162b2 vaccination were evaluated in a total of 187 patients either with allogeneic hematopoietic transplantation, with renal transplantation, with anti-CD20 antibody therapy, or with anti-CD38 antibody therapy, and in 66 healthy controls. The early response at one to three months after vaccination was significantly inferior among patients with renal transplantation, patients with anti-CD20 antibody therapy, and patients with anti-CD38 antibody therapy in comparison to healthy control. But the patients with allogeneic hematopoietic transplantation showed early humoral response comparable to healthy control. The late response at 6 months after vaccination was still suboptimal among patients with renal transplantation and patients with anti-CD20 therapy. Among our patient group, renal transplant recipients had the lowest antibody titers after vaccination regardless of timing of vaccination. Patients who had received allogeneic hematopoietic transplantation attained a comparable serological response to the control group especially if they are vaccinated >300 days after transplantation, but the response was suboptimal if the vaccination was within 300 days after transplantation. Our results may provide policy makers with critical information for the further stratification of at-risk groups, helping contribute to a better allocation of resources, including additional booster vaccination.

Keywords: Anti-CD20 antibody; COVID-19; Hematopoietic transplantation; Kidney transplantation; Vaccination.

Graphical abstract

Fig. 1

A comparative analysis of the antibody responses to BNT162b2 RNA vaccines. The neutralizing antibody (NA) titers at the early phase (1–3 months after the second vaccination) (a, c), and at the late phase (6 months after the second vaccination) (b, d), are depicted. In the early phase, the median titers of the patients and controls were 322.5 (6.8–57,100) AU/mL and 4840 (474–27,800) AU/mL, respectively (p = 1.44E-10). In the late phase the median titers of the patients and controls were while they were 141 (6.8–3960) AU/mL and 1080 (218 to 4000) AU/mL, respectively (p = 3.25 × 10E-7). More specifically, patients who had received renal transplantation (p = 5.73 × E-12), anti-CD20 antibody therapy (p = 1.75 × E-8) or anti-CD38 antibody therapy (p = 3.55 × E-3) showed significantly inferior NA responses in the early phase, while patients who had received renal transplantation (p = 7.98 × E-4) and anti-CD20 antibody therapy (p = 9.85 × E-4) showed suboptimal NA responses in the late phase. The allo-HCT recipient group attained comparable serological responses.

Fig. 2

The NA titers at the early phase were depicted with different underlying causes as well as different timings of vaccination after each of the treatment/transplantation. Those vaccinated 300 days after hematopoietic transplantation or anti-CD20 antibody treatment attained more favorable humoral responses in comparison to those vaccinated within 300 days or controls. Abbreviations: E. early phase; L. late phase.