BACKGROUND: Since 2019, PCV13 has replaced PCV10 in Belgium’s childhood vaccination program, reducing IPD cases caused by PCV13 serotypes, mainly 19A, but accompanied by serotype replacement. This changing epidemiology prompted consideration of the higher-valent PCV20 vaccine. Despite broader serotype coverage, clinical effectiveness against certain serotypes remains uncertain, raising concerns about vaccine failures. To date, vaccine failures and breakthrough infections have not been systematically studied in Belgium. This study aims to establish a baseline by characterizing vaccine failures and breakthrough infections in children 0-5 years old during the recent PCV13 era, providing a reference point ahead of PCV20 introduction.

METHODS: We conducted a retrospective cohort study including children ≤5 years diagnosed with IPD in Belgium from 2019 to 2024, using surveillance data from the National Reference Centre for invasive pneumococci and the PediSurv network. Vaccine failures and breakthrough infections were identified and characterized by serotype and clinical characteristics.

RESULTS: Of 543 pediatric IPD cases with known vaccination status, 451 (83 %) had received at least one dose of pneumococcal conjugate vaccine. Among these, we identified 26 vaccine failures (5.8 %) and 37 breakthrough infections (8.2 %). Differences in breakthrough proportions between PCV10 and PCV13 were primarily driven by PCV13-exclusive serotypes, after adjustment no significant differences remained. Vaccine failures were caused by serotypes 19A (61.5 %), 3 (26.9 %), and 14 (11.5 %), and were associated with older age (OR: 1.49; 95 % CI: 1.18-1.89) and invasive pneumonia (OR: 3.89; 95 % CI: 1.66-9.12). Breakthrough infections involved serotypes 19A (70.3 %), 3 (13.5 %), 14 (13.5 %), and 19F (2.7 %) and occurred more often in younger children (OR: 0.61; 95 % CI: 0.42-0.87).

CONCLUSION: These findings provide the first national baseline of vaccine failures, offering a reference point for evaluating PCV20 introduction. Continued monitoring will be essential to assess the real-world impact of higher-valent pneumococcal vaccines and to guide evidence-based vaccination policy.