Comparative Analysis of Pneumococcal Serotypes over a 10-Year Period (2014–2024) in the Comunidad Valenciana Region and Their Relationship with PCV13, PCV20 and PCV21

Background/Objectives: This study analyzes the epidemiology of invasive pneumococcal disease (IPD) and the dynamics of Streptococcus pneumoniae serotypes in the Comunidad Valenciana (CV), Spain, over a 10-year period (2014–2024), with particular focus on vaccine coverage and effectiveness of PCV13 compared to the newer PCV20 and PCV21 formulations. Methods: A total of 2,014 isolates were collected from sterile clinical samples and characterized by serotype, patient demographics, and vaccination status. Results: Overall vaccination coverage was low (22.6%), with the highest rates observed in children under 10 years (78%) compared to only 16% in those aged 10–64 years and 22% in those over 64. Serotype distribution revealed 120 distinct serotypes, with serotype 8 (17.6%) and serotype 3 (14.7%) being the most frequent. Serotype 8 predominated among unvaccinated individuals, while serotype 3 remained highly prevalent despite inclusion in PCV13, reflecting limited vaccine effectiveness. Other relevant serotypes included 22F, 9N, 19A, 6C, and 23A. Temporal analysis showed increases in serotypes 8, 3, and 23A in recent years, while 9N, 19A, 15A, and 11A significantly declined. Among serotypes with <2% incidence, some such as 4, 12F, 16F, and 24F showed upward trends. Conclusions: The findings suggest that PCV20 currently provides broad coverage of dominant serotypes, but PCV21 may offer advantages should serotypes like 23A, 9N, or 15A increase further due to serotype replacement. Continuous epidemiological surveillance is essential to guide evidence-based vaccine policy and anticipate future vaccine reformulations.