Coadministration of 13-valent pneumococcal conjugate and quadrivalent inactivated influenza vaccines in adults previously immunized with polysaccharide pneumococcal vaccine 23: a randomized clinical trial.

Immune responses to 13-valent pneumococcal conjugate vaccine (PCV13) and quadrivalent inactivated influenza vaccine (QIV) in older adults may vary with coadministration and previous pneumococcal polysaccharide vaccination. This study assessed safety and noninferiority of immune responses to coadministered PCV13 and QIV compared with each vaccine given alone. Adults ≥50 years old preimmunized with ≥1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) ≥1 year before enrollment were randomized 1:1 to receive PCV13+QIV then placebo 1 month later or placebo+QIV then PCV13 1 month later. Administration of PCV13 and placebo was blinded; QIV was administered open-label. Pneumococcal serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) 1 month after PCV13, and influenza hemagglutination inhibition assay GMTs 1 month after QIV were measured. Prespecified noninferiority was demonstrated by a lower bound of the 2-sided 95% CI for geometric mean ratios >0.5. Safety endpoints included proportions of subjects with adverse and serious adverse events. Of 882 randomized subjects, 846 comprised the evaluable immunogenicity population. Immune responses to all 13 pneumococcal serotypes and all 4 influenza strains 1 month after PCV13+QIV were noninferior to responses 1 month after each vaccine given alone. No safety concerns were identified. Immune responses to coadministered PCV13 and QIV were noninferior to responses after each vaccine given alone, although generally lower for coadministered PCV13. PCV13 and QIV can be administered concomitantly to adults ≥50 years of age preimmunized with PPSV23.

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.

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.