Protection and Duration of 23-Valent Pneumococcal Polysaccharide Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older Adults with Low Vaccination Coverage: A Multicenter Matched Case–Control Study in China

Background/Objectives: 23-valent pneumococcal polysaccharide vaccine (PPV23) effectiveness against community-acquired pneumonia (CAP) remains controversial, with critical gaps in low-coverage settings and beyond 5 years post-vaccination. We estimated real-world PPV23 effectiveness against CAP hospitalization and characterized its duration among elderly adults in a low-coverage region. Methods: A multicenter matched case–control study was conducted across 14 hospitals in Eastern China (2018–2022). Cases were patients aged ≥ 60 years hospitalized with clinically diagnosed CAP. Up to three controls per case were matched on sex, age (±3 years), admission date (±5 days), hospital, and residential community. Conditional logistic regression estimated vaccine effectiveness (VE), adjusting for chronic comorbidities and healthcare utilization. Results: Among 6645 cases and 15,806 controls, 5-year PPV23 coverage was 2.14% (cases) and 2.76% (controls). PPV23 was associated with a 22.5% reduction in CAP hospitalization (adjusted VE = 22.5%, 95% CI: 4.1% to 37.3%). Protection was concentrated in non-severe CAP (adjusted VE = 25.7%, 95% CI: 7.0% to 40.7%), with no significant effect in severe CAP (adjusted VE = −11.7%, 95% CI: −115.1% to 42.0%). Extending the exposure window to 6 years yielded no significant VE (adjusted VE = 17.3%, 95% CI: −1.8% to 32.8%). Conclusions: PPV23 provides meaningful protection against CAP hospitalization in elderly adults in low-coverage settings, only for non-severe disease. Waning efficacy beyond 5 years supports revaccination at that interval.