Antibody and Plasmablast Response to 13-Valent Pneumococcal Conjugate Vaccine in Chronic Lymphocytic Leukemia Patients – Preliminary Report

Abstract

BackgroundChronic 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.MethodsBoth 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.ResultsAdequate 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.ConclusionsPCV13 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.

Influenza and pneumococcal vaccination in hematological malignancies: a systematic review of efficacy, effectiveness and safety

“…Pasiarsky and colleagues in a recent work analyze antibody and plasmablast response to 13–valent pneumococcal conjugate vaccine in Chronic Lymphocytic Leukemia Patients 53. They evaluated 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.…”

Bacterial Pneumonia in Patients with Cancer

“…Interestingly, in this population, antibody responses to PSV23 positively correlate with hematologic response to chemotherapy [85]. The conjugated 13-valent pneumococcal vaccination (PCV13) depends more heavily upon T-cell responses, and remains more immunogenic in many immunocompromised cancer populations [86-88]. …”

Perturbation of the normal immune system in patients with CLL

“…41 Unfortunately, modern conjugated vaccine preparations, which recruit T-cell "help" are still not generally capable of fully overcoming suboptimal immune responses. 44 In a recent study, an adequate response to an initial dose of 13-valent pneumococcal conjugate vaccine was found in only 58% of CLL patients compared with all healthy age-matched controls. 44 This study also observed a very poor increment of plasmablasts within peripheral blood at 1 week after vaccination.…”

“…44 In a recent study, an adequate response to an initial dose of 13-valent pneumococcal conjugate vaccine was found in only 58% of CLL patients compared with all healthy age-matched controls. 44 This study also observed a very poor increment of plasmablasts within peripheral blood at 1 week after vaccination. Overall the clinical observations suggest that both a direct suppression of B-cell function and an impairment of cognate T-cell help contribute to the poor response to vaccines.…”