PCV13 Plus PPSV23 Vaccination Recommended for Patients With Sickle Cell Disease

The 13-valent conjugate pneumococcal vaccine (PCV13) followed by the 23-valent polysaccharide vaccine (PPSV23) for protection against pneumococcal disease improves antibody responses to a large range of pneumococcal serotypes among adults with sickle cell disease (SCD). These findings were published in Clinical Infectious Diseases.

Patients with major SCD at Henri Mondor Hospital in France were enrolled in this open-label, phase 2 study between 2013 and 2017. Patients were randomly assigned to receive PPSV23 at week 4 either with or without PCV13 at baseline. Safety and humoral immunity through week 96 were evaluated, and the primary endpoint was the number of patients who experienced a 4-fold increase in serotype-specific immunoglobulin (Ig)G antibody levels to at least 10 pneumococcal serotypes between baseline and week 8. The primary efficacy analysis was performed among a modified intention-to-treat population, defined as patients who received at least 1 vaccine dose.

Among patients who received either PCV13 plus PPSV23 (n=63) or PPSV23 alone (n=65), the mean age was 39.2±10.6 and 38.7±10.3 years, 54.0% and 50.8% were women, 68.2% and 72.3% had hemoglobin SS SCD, 23.8% and 23.1% had hemoglobin SC SCD, and 98.4% and 98.4% had anemia, respectively.

A significantly higher percentage of patients in the PCV13 plus PPSV23 vs PPSV23 alone groups experienced a 2-fold increase in antibody titers to at least 10 pneumococcal serotypes at weeks 8 (47.4% vs 19.7%; P <.001), 24 (41.7% vs 23.6%; P =.050), and 96 (38.7% vs 13.5%; P =.017). In addition, a significantly higher percentage of patients in the PCV13 plus PPSV23 vs PPSV23 alone groups experienced a 4-hold increase in antibody titers to at least 10 serotypes at week 8 (24.6% vs 8.2%; P =.016).

Overall, receipt of PCV13 plus PPSV23 vs PPSV23 alone elicited improved antibody responses to 0 to 1 (15.8% vs 52.5%), 2 to 5 (35.1% vs 31.1%), 6 to 9 (24.6% vs 8.2%), and 10 to 12 (24.6% vs 8.2%) pneumococcal serotypes.

At baseline, the geometric mean concentrations of the 13 evaluated IgG antibodies did not differ between the 2 patient groups. At week 8, the PCV13 plus PPSV23 regimen was associated with significantly higher concentrations of IgG-4, IgG-6A, Igg-6B, IgG-9V, IgG-14, IgG-19A, IgG-19F, and IgG-23F antibodies compared with PPSV23 alone (all P £.042). At week 96, higher concentrations of 6 of the IgG antibodies persisted among recipients of PCV13 plus PPSV23 compared with recipients of PPSV23 alone (all P £.033).

In a subgroup analysis, no significantly predictive factors for immunologic response to vaccination were observed. However, immunologic responses following receipt of PCV13 plus PPSV23 tended to be decreased among women (P =.10) and those who received treatment with hydroxycarbamide (P =.08).

Overall, there were 26 reports of injection site pain and 22 severe adverse events, although none were related to vaccination. A total of 11 acute chest syndrome and 6 pneumonia events also occurred.

The major limitation of this study was that time since last PPSV23 vaccination was only recorded for a subset of patients.

According to the researchers, “The demonstration of the superior immunogenicity of the PCV13/PPSV23 regimen, both in terms of magnitude and functionality, in adults with SCD supports evidence for the application of guidelines of this regimen.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.