Immunogenicity and safety of double dosage of pneumococcal vaccines in adult kidney transplant recipients and waiting list patients: A non-blinded, randomized clinical trial

• Published in: Vaccine 2022-06, Vol.40 (28), p.3884-3892
• Main Authors: Larsen, Lykke, Bistrup, Claus, Sørensen, Søren Schwartz, Boesby, Lene, Jørgensen, Charlotte Sværke, Johansen, Isik Somuncu
• Format: Article
• Language: English
• Subjects: Adults; Age; Aluminum; Antibodies; Clinical trials; Consent; Cytomegalovirus; Dosage; Immunogenicity; Immunoglobulin G; Immunosuppressive agents; Kidney transplant recipient; Kidney transplantation; Kidney transplants; Kidneys; Patients; Phenols; Pneumococcal conjugate vaccine; Pneumococcal polysaccharide vaccine; Polysaccharides; Sample size; Serotypes; Statistical analysis; Vaccines; Variables
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2022.05.040

•Pneumococcal prime-boost vaccination is recommended for transplant recipients/candidates.•23-valent polysaccharide vaccine is additive in kidney transplant recipients/candidates.•In candidates, double dosage vaccines are superior to normal dosage.•Double dosage pneumococcal vaccines are safe. Pneumococcal prime-boost vaccination is recommended for solid organ transplant recipients, but is not thoroughly tested in this population. Furthermore, a pneumococcal vaccine dose effect has never been investigated, though observed in healthy adults. To assess whether a double dose of 13-valent pneumococcal conjugate vaccine (PCV13) and of 23-valent pneumococcal polysaccharide vaccine (PPV23) increases the immunogenicity of prime-boost vaccination in kidney transplant recipients (KTRs) and patients on the kidney transplant waiting list (WLPs), a phase 3, randomized, non-blinded trial was conducted. KTRs and WLPs were in parallel groups assigned either normal or double dosage of both vaccines 12 weeks apart. A ′protective response′ was an average geometric mean concentration ≥ 1 mg/L based on 12 vaccine shared serotype-specific IgG antibodies. Furthermore, number of antibodies with ≥ 2-fold rises and individual serotype-specific antibody concentrations were evaluated. Follow-up was 48 weeks. Seventy-four KTRs and 65 WLPs were enrolled. In WLPs, double dosage resulted in a significantly higher proportion of participants with a ′protective response′ (66.7%), 5 weeks after PPV23, compared to normal dosage (35.5%), p = 0.015. KTRs exhibited no dose effect. After PPV23, all four groups had increased their number of serotypes with ≥ 2-fold rises (p ≤ 0.05 for both WLPs groups; p ≤ 0.01 for both KTRs groups). Vaccines were safe, well tolerated and still immunogenic at week 48. Data suggests that double dosage of pneumococcal vaccines used according to the prime-boost strategy might be recommendable for WLPs. Furthermore, our data supports PPV23́s additive effect to PCV13 in KTRs and WLPs. (EudraCT: 2016–004123-23)