Immunogenicity, Safety, and Tolerability of 13-Valent Pneumococcal Conjugate Vaccine Followed by 23-Valent Pneumococcal Polysaccharide Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged ≥2 Years: An Open-Label Study
Open Access
- 13 April 2015
- journal article
- clinical trial
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 61 (3), 313-323
- https://doi.org/10.1093/cid/civ287
Abstract
Background. Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention. Methods. In an open-label study, patients (n = 251) 3–6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed. Results. In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99–23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00–6.97), and little change after PPSV23 (GMFR range, 0.86–1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barré syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines. Conclusions. A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable. Clinical Trials Registration. NCT00980655.Keywords
Funding Information
- Pfizer Inc.
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