Antibody and plasmablast response to 13-valent pneumococcal conjugate vaccine in chronic lymphocytic leukemia patients--preliminary report

Abstract

Background: Chronic lymphocytic leukemia (CLL) leads to significant immune system dysfunction. The predominant clinical presentation in 50% of patients involves recurrent, often severe, infections. Infections are also the most common (60-80%) cause of deaths in CLL patients. The scope of infections varies with the clinical stage of the disease. Treatment-naive patients typically present with respiratory tract infections caused by encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. Since 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in the United States and some EU countries for pneumococcal infection prevention in patients with CLL (besides the long-standing standard, 23-valent pneumococcal polysaccharide vaccine, PPV23). The aim of this study was to compare the immune response to PCV13 in 24 previously untreated CLL patients and healthy subjects.

Methods: Both groups were evaluated for: the levels of specific pneumococcal antibodies, the levels of IgG and IgG subclasses and selected peripheral blood lymphocyte subpopulations including the frequency of plasmablasts before and after immunization.

Results: Adequate response to vaccination, defined as an at least two-fold increase in specific pneumococcal antibody titers versus pre-vaccination baseline titers, was found in 58.3% of CLL patients and 100% of healthy subjects. Both the CLL group and the control group demonstrated a statistically significant increase in the IgG2 subclass levels following vaccination (P = 0.0301). After vaccination, the frequency of plasmablasts was significantly lower (P<0.0001) in CLL patients in comparison to that in controls. Patients who responded to vaccination had lower clinical stage of CLL as well as higher total IgG, and IgG2 subclass levels. No significant vaccine-related side effects were observed.

Conclusions: PCV13 vaccination in CLL patients is safe and induces an effective immune response in a considerable proportion of patients. To achieve an optimal vaccination response, the administration of PCV13 is recommended as soon as possible following CLL diagnosis.

Figure 1. Specific antipneumococcal antibody titers before and after PCV13 vaccination in: (a) the control group and (b) CLL patients (P<0.001, and P<0.001, respectively).

Proportion of plasmablasts before and after PCV13 vaccination in: (c) the control group and (d) CLL patients (P = 0.001, and P = 0.0266, respectively). Serum IgG2 levels before and after PCV13 vaccination in: (e) the control group and (f) CLL patients (P = 0.0166, and P = 0.012, respectively). A multiparameter flow cytometric analysis of the percentages of plasmablasts before and 7 days after vaccination. Representative example of gating on CD19+ B-cell subpopulations. Percentages of cells in the different quadrants are shown. CD19+/IgD−/CD27++ plasmablasts (upper left quadrant) and CD19+/IgM/CD38++ plasmablasts (lower left quadrant) before vaccination and CD19+/IgD−/CD27++ plasmablasts (upper right quadrant) and CD19+/IgM/CD38++ plasmablasts (lower right quadrant) after vaccination in: (g) the individual CLL patient who did not respond to PCV13 administration and (h) the individual healthy subject from the control group, who responded to PCV13 administration.