Revaccination with pneumococcal conjugate vaccine five years after primary immunization improves immunity in patients with chronic lymphocytic leukemia

Abstract

Patients with chronic lymphocytic leukemia (CLL) have an impaired response to vaccination, which calls for improved vaccination strategies. This study aimed to evaluate antibody persistence 5 years after pneumococcal vaccination and response to revaccination. Seventy-four CLL patients and 31 controls, all primary immunized with 13-valent conjugated pneumococcal vaccine (PCV13) or 23-valent polysaccharide vaccine (PPSV23), were included. Antibody persistence was assessed, followed by revaccination with PCV13 and a second revaccination with PCV13 or PPSV23. Serological protection, defined as a serum serotype-specific IgG concentration ≥0.35 μg/mL for ≥70% of shared serotypes, did not differ significantly in CLL patients primary immunized with PCV13 or PPSV23 (relative risk ratio [RR]=2.7, 95% confidence interval [95% CI]: 0.5-13.1), but was lower in patients than in controls (10% vs. 32%; RR=0.3; 95% CI: 0.1-0.7). Following revaccination with PCV13, serological response, defined as a ≥2-fold increase for ≥70% of shared serotypes, was 24% in patients primary immunized with PCV13 compared to 12% in those primary immunized with PPSV23 (RR=2.0; 95% CI: 0.6-6.9). A second revaccination with PCV13 significantly improved serological response while PPSV23 did not further improve immunity. Our findings suggest that repeated doses of a T-cell-dependent pneumococcal vaccine improve protection in CLL patients. The study is registered at www.clinicaltrials.gov (NCT05316831).

Figure 1.

Study design, study population and revaccination strategy among patients with chronic lymphocytic leukemia and immunocompetent controls. CLL: chronic lymphocytic leukemia; PCV13: 13-valent conjugated pneumococcal vaccine; PPSV23: 23-valent polysaccharide vaccine.

Figure 2.

Serological response and protection in patients with chronic lymphocytic leukemia. (A) Serological response (SR) in group A and group B after revaccination 1, after revaccination 2 and 12 months after revaccination 1. SR defined as a 2-fold increase above IgG levels ≥0.35 μg/mL in at least nine (70%) of the 12 serotypes compared to baseline. (B) Serological protection (SP) in group A and group B before revaccination (5 years after primary immunization), after revaccination 1, after revaccination 2 and 12 months after revaccination 1. SP defined as ≥0.35 μg/mL for at least nine (70%) of the 12 serotypes. (C) SP in group A and group B before revaccination (5 years after primary immunization), after revaccination 1, after revaccination 2 and 12 months after revaccination 1. SP defined as ≥1.3 μg/mL for at least nine (70 %) of the 12 serotypes. 95% CI: 95% confidence interval; CLL: chronic lymphocytic leukemia; PCV13: 13-valent conjugated pneumococcal vaccine; PPSV23: 23-valent polysaccharide vaccine; wk: weeks; mo: months; revacc: revaccination.

Figure 3.

Serological response and protection in patients with chronic lymphocytic leukemia and controls. (A) Serological response (SR) in patients with chronic lymphocytic leukemia (CLL) and controls after revaccination 1 and 12 months after revaccination. SR defined as a 2-fold increase above IgG levels ≥0.35 µg/mL for at least nine (70%) of the 12 serotypes compared to baseline. (B) Serological protection (SP) in CLL patients and controls 5 years after primary immunization, after revaccination 1 and 12 months after revaccination. SP defined as ≥0.35 µg/mL for at least nine (70%) of the 12 serotypes. (C) SP in CLL patients and controls 5 years after primary immunization, after revaccination 1 and 12 months after revaccination. SP defined as ≥1.3 µg/mL for at least nine (70%) of the 12 serotypes. 95% CI: 95% confidence interval; PCV13: 13-valent conjugated pneumococcal vaccine; PPSV23: 23-valent polysaccharide vaccine; wk: weeks; mo: months; revacc: revaccination.