Humoral immune response to tick-borne encephalitis vaccination in allogeneic blood and marrow graft recipients

Abstract

The aim of this prospective study was to characterize the humoral immune response to TBE vaccination after hematopoietic stem cell transplantation (HSCT). Nineteen adult patients 11-13 months after HSCT and 15 age-matched immunocompetent adults received up to three TBE vaccinations. Antibodies against TBE virus were measured by neutralization test (NT). As primary endpoint, the antibody response (NT titer of ≥10 and at least a twofold increase from baseline 4 weeks after second vaccination) was compared between patients and controls using Fisher exact test. Prior vaccination, 15 (79%) HSCT patients still had detectable neutralizing antibodies. At primary endpoint, the antibody response was significantly lower in patients than in controls (35% versus 93%; p < 0.001). The CD4+ cell count was a predictor for an antibody response in patients (p = 0.019). Interestingly, the majority of HSCT patients still had detectable antibodies prior vaccination. Following vaccination, antibody response in HSCT patients was associated with the CD4+ cell count.

Keywords: Haematological cancer; Inactivated vaccines; Viral infection.

Conflict of interest statement

Competing interestsC.F. received a grant of the Austrian Science Fund (grant number KLI 372) that enabled to conduct the present study and partly supported employment of N.H. H.B. received a research grant from Pfizer (Project No. WI201689), who performed neutralization assays and supplied TBE vaccines free of cost. Pfizer had no role in the conceptualization, design of the study or the decision to publish. All other authors report no competing interests related to the present work.

© The Author(s) 2020.

Figures

Fig. 1. Flow chart of the study population depicting screening, entrollment and loss to follow-up.

In the flow chart the number of patients who were screened for this study and the reasons for exclusion are documented. Number of patients and healthy controls who received one, two or all three vaccinations and the number of patients/healthy controls who were lost to follow-up at each step of the study are depicted. aThe total number of individuals screened for eligibility was not recorded.

Fig. 2. Assessment of geometric mean and individual NT titers.

Geometric mean NT titers (filled triangles and circles) and individual titers (blank circles) of patients (red) versus controls (black) at pretransplant, at baseline 1 year after HSCT, 4 weeks after second vaccination, and 4 weeks after third vaccination.

Fig. 3. Assessment of geometric mean fold and individual NT titer rises.

Geometric mean fold rises of NT titers (bars) and individual rises (circles) from baseline to 4 weeks after second vaccination and from baseline to 4 weeks after third vaccination comparing patients (red) with healthy controls (black) with corresponding p values.