Effectiveness of vaccine dosing schedules for pneumococcal invasive disease in children: A systematic review and meta-analysis

Invasive pneumococcal disease (IPD) persists despite the effectiveness of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV). As the protection offered by different dosing regimens remains uncertain, we evaluated the vaccine effectiveness (VE) against vaccine-type (VT) IPD in children based on the number of vaccine doses. We searched MEDLINE/Embase/Web of Science/CENTRAL databases from January 2000 to December 2024 for studies on PCV7 and/or PCV13 VE against VT-IPD in children ≤18 years. VE estimates were recorded by vaccination status at IPD onset, classified into four groups (1) primary + booster group (1–3 primary doses <12 months of age plus 1 booster dose ≥12 months), (2) 1 primary dose group, (3) 2 primary doses group, and (4) 3 primary doses group (primary doses given <12 months of age and no booster). From 1982 studies, 25 studies were included, reporting 525 cases in the primary + booster group and 821 cases in the 1–3 primary dose(s) groups. Pooled VE from 14 studies was 94.4 % for the primary + booster group, and 66.8 %, 78.8 %, and 82.0 % for the 1-, 2-, and 3- primary dose(s) groups, respectively. Among VT-IPD breakthrough cases, serotype 19 A was most common (27.9 %), followed by 19F (20.5 %) and 3 (18.9 %). Sensitivity analyses showed a VE of ~95 % for the 2 + 1 and 3 + 1 schedules, versus 78.9 % for 3 + 0. Our findings strongly support schedules that include a booster dose, such as the 2 + 1 regimen, as an optimal strategy for preventing VT-IPD in children. • Pneumococcal conjugate vaccines are highly effective in preventing IPD in children. • A single primary dose is less effective than two or three primary doses. • Two primary doses provide similar protection to three primary doses. • The booster dose is critical for maximizing effectiveness against VT-IPD.