Abstract
Background
Patients with sickle-cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD.
Methods
This was a randomized open-labelled phase 2 study of the immunogenicity of PCV13 at week (W)0, followed by PPSV23 at W4, compared to PPSV23 alone at W4 in adult patients with SCD. The proportion of responders (four-fold increase of serotype-specific IgG antibodies) to at least 10-shared serotypes was assessed at W8. Secondary endpoints were: i) geometrical mean titers (GMTs), ii) responders to 0-1, 2-5, 6-9, and 10-12 serotypes, iii) pneumococcal opsonophagocytic (OPA) activity, and iv) response durability at W24 and W96.
Results
In total, 128 patients were randomized in the PCV13/PPSV23 (n=63) or PPSV23-alone groups (n=65). At W8, 24.5 6% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary endpoint (p=0.016). These numbers were 36.2% and 8.7% for OPA responders (p=0.002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0-1, 2-5, 6-9, and 10-12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At W96, GMTs were significantly higher in the PCV13/PPSV23 than in the PPSV23 alone group for five serotypes (4, 14, 19A, 19F, 23F).
Conclusions
A PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.Clinical Trial Registration: NCT02274415
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