A randomized trial of simultaneous versus sequential pneumococcal vaccination in elderly.

Objectives: To evaluate whether simultaneous vaccination of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) elicits higher antigen-specific memory B cell responses compared to sequential (PCV13 followed by PPSV23 after 6 months) or single PPSV23 vaccination in elderly.

Methods: In this monocentric, randomized trial, vaccine-naïve adults aged ≥60 years were assigned 1:1:1 to a simultaneous, sequential or single vaccination group. The primary outcome was the change in memory B cells specific for four vaccine-serotypes (ST3, ST14, ST19A, and ST23F) at 27 to 28 weeks after first vaccine dose compared to baseline. Secondary outcomes assessed safety, serotype-specific immunoglobuin G geometric mean fold rise (GMFR) and memory B cells over a 24-month period.

Results: Total of 123 persons (41 per group, 65.2 ± 4.4 years, 61.8% females) were randomized. Among 118 evaluable persons, median changes (95% CI) in memory B cells relative to total B cells from baseline to week 27 to 28 were most pronounced for ST19A with 0.022% (0.002%-0.045%) in the simultaneous, 0.022% (-0.006% to 0.068%) in the sequential, and 0.005% (-0.004% to 0.054%) in the single group. There was no evidence of a significant difference in memory B cell responses across all four vaccine-serotypes induced by simultaneous when compared with sequential or single vaccination (e.g. Hodges-Lehmann [HL-] estimator for ST19A, -0.007% [95% CI, -0.038% to 0.021%] for simultaneous vs. sequential; 0.009% [95% CI, -0.017% to 0.036%] for simultaneous versus single), at primary endpoint. Six months after completing the full vaccination schedule, memory B cell response for ST19A was lower in simultaneous than sequential group (HL-estimator, -0.039%; 95% CI, -0.071% to -0.010%). At 24 months, sequential vaccination achieved higher immunoglobulin G against ST3 (GMFR 5.17) than simultaneous (GMFR 2.82) or single vaccination (GMFR 1.94). No serious adverse events occurred.

Conclusion: Simultaneous vaccination did not elicit higher memory B cell responses compared to sequential or single vaccination. All approaches were safe.