Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against vaccine serotype pneumococcal pneumonia in adults: a case-control test-negative design study

Background: Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is available in the UK to adults aged 65 years or over and those in defined clinical risk groups. We evaluated the vaccine effectiveness (VE) of PPV23 against vaccine-type pneumococcal pneumonia in a cohort of adults hospitalised with community-acquired pneumonia (CAP).Methods and Findings: Using a case-control test negative design, a secondary analysis of data from a prospective cohort study of adults (aged ? 16 years) hospitalised at two university teaching hospitals in Nottingham, England with CAP from September 2013 to August 2018 was conducted. The exposure of interest was PPV23 vaccination at any time point prior to the index admission. A case was defined as a patient with PPV23 serotype-specific pneumococcal pneumonia; a control as non-PPV23 serotype pneumococcal pneumonia or non-pneumococcal pneumonia. Pneumococcal serotypes were identified from urine samples using a multiplex immunoassay or from positive blood cultures. Multivariable logistic regression was used to derive adjusted odds of case status between vaccinated and unvaccinated individuals; VE estimates were calculated as (1-odds ratio) x100%. Of 2357 patients there were 717 PPV23 cases (48% vaccinated) and 1640 controls (54.5% vaccinated). The adjusted VE (aVE) estimate against PPV23 serotype disease was 24% (95%CI 5 to 40%, p=0.02). Estimates were similar in analyses restricted to vaccine eligible patients (n=1768, aVE 23%, 95%CI 1 to 40%) and patients aged ?65 years (n=1407, aVE 20%, 95% CI -5 to 40), but not in patients aged ?75 years (n=905, aVE 5%, 95%CI -37 to 35%). Adjusted VE in relation to PPV23/non-PCV13 serotype pneumonia (n=417 cases, 43.7% vaccinated) was 29% (95%CI 6 to 46%). Key limitations of this study are that due to high vaccination rates, there was a lack of power to reject the null hypothesis of no vaccine effect; and that the study was not large enough to allow robust subgroup analysis in the older age groups. Conclusion: In the setting of an established national childhood PCV13 vaccination programme, PPV23 vaccination of clinical at-risk patient groups and adults ? 65 years provided moderate long-term protection against hospitalisation with PPV23 serotype pneumonia. These findings suggest PPV23 vaccination may continue to have an important role in adult pneumococcal vaccine policy, including the possibility of re-vaccination of older adults.