Immunogenicity of the 13-Valent Pneumococcal Conjugated Vaccine Followed by the 23-Valent Polysaccharide Vaccine in Chronic Lymphocytic Leukemia

Abstract

Patients with Chronic Lymphocytic Leukemia (CLL) have a 29- to 36-fold increased risk of invasive pneumococcal disease (IPD) compared to healthy adults. Therefore, most guidelines recommend vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by the 23-valent polysaccharide vaccine (PPSV23). Because both CLL as well as immunosuppressive treatment have been identified as major determinants of immunogenicity, we aimed to assess the vaccination schedule in untreated and treated CLL patients. We quantified pneumococcal IgG concentrations against five serotypes shared across both vaccines, and against four serotypes unique to PPSV23, before and eight weeks after vaccination. In this retrospective cohort study, we included 143 CLL patients, either treated (n = 38) or naive to treatment (n = 105). While antibody concentrations increased significantly after vaccination, the overall serologic response was low (10.5%), defined as a ≥4-fold antibody increase against ≥70% of the measured serotypes, and significantly influenced by treatment status and prior lymphocyte number. The serologic protection rate, defined as an antibody concentration of ≥1.3 µg/mL for ≥70% of serotypes, was 13% in untreated and 3% in treated CLL patients. Future research should focus on vaccine regimens with a higher immunogenic potential, such as multi-dose schedules with higher-valent T cell dependent conjugated vaccines.

Keywords: antibody response; chronic lymphocytic leukemia; immunogenicity; pneumococcal vaccination.

Figure 1

Vaccination and measurement schedule. Patients were retrospectively included when the vaccination and measurement schedule was completed. According to the current local standard of care for immunosuppressed individuals, prior to vaccination, blood was collected to determine serotype-specific pneumococcal antibodies. Post: collection of serum 8 weeks post-immunization; Pre: collection of serum prior to vaccination.

Figure 2

Antibody dynamics of CLL patients after the combined vaccination schedule (PCV13/PPSV23). Antibody concentrations against the five shared serotypes (PCV13/PPSV23) (serotypes highlighted with the grey bar below) and four serotypes unique to PPSV23 (orange bar below serotypes) for each individual CLL patient are shown in the figure. Each grey line indicates the antibody dynamics of one patient from pre- to post-immunization. Median antibody concentration and gradient between pre- and post-vaccination titer are indicated for the overall group (thick orange line), the treatment naive individuals (blue) and treated individuals (red). The upper dotted line indicates 1.3 μg/mL, cut-off for serologic protection, and the lower dotted line indicates 0.35 μg/mL according to the WHO threshold for protection. p-values are calculated to determine the median difference between pre- and post-immunization concentration for each serotype, using the Wilcoxon Signed Rank test for related samples. Pre: antibody concentration prior to vaccination; Post: antibody concentration eight weeks post-immunization.