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

Author summary Why was this study done? is the commonest bacterial cause of community-acquired pneumonia (CAP) worldwide with over 90 different serotypes. A 23-valent pneumococcal polysaccharide vaccine (PPV23) targeting 23 common serotypes is recommended for use in adults in various countries to protect against pneumococcal infection. The long-term vaccine effectiveness (VE) of PPV23 against vaccine serotype pneumococcal CAP in adults in the setting of an established childhood pneumococcal vaccine programme is not known. What did the researchers do and find? We retrospectively analysed data from a cohort of adults hospitalised with CAP in Nottingham, England, who had a diagnostic blood or urine test to determine (i) whether they had pneumococcal disease and (ii) if so, whether or not it was a serotype covered by the PPV23 vaccine. We calculated the VE of PPV23 in our cohort by calculating the odds of infection with vaccine-type pneumococcal pneumonia (cases) versus pneumonia of an alternate cause (controls) between vaccinated and unvaccinated individuals. In our group of 2,357 patients (717 PPV23 cases, 1,640 controls) with an average time of 10 years since PPV23 vaccination, we estimated the VE of PPV23 against PPV23 serotype pneumonia to be 24% after adjustment for patient factors (95% CI 5%-40%, = 0.02). What do these findings mean? PPV23 vaccination provides moderate long-term protection against hospitalisation with PPV23 serotype pneumonia. PPV23 vaccination may continue to have an important role in national pneumococcal immunisation policies, including the possibility of revaccination of older adults. Background Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is available in the United Kingdom to adults aged 65 years or older 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 was conducted from a prospective cohort study of adults (aged >= 16 years) with CAP hospitalised at 2 university teaching hospitals in Nottingham, England, from September 2013 to August 2018. The exposure of interest was PPV23 vaccination at any time point prior to the index admission. A case was defined as PPV23 serotype-specific pneumococcal pneumonia and a control as non-PPV23 serotype pneumococcal pneumonia or nonpneumococcal 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) x 100%. Of 2,357 patients, there were 717 PPV23 cases (48% vaccinated) and 1,640 controls (54.5% vaccinated). The adjusted VE (aVE) estimate against PPV23 serotype disease was 24% (95% CI 5%-40%, p = 0.02). Estimates were similar in analyses restricted to vaccine-eligible patients (n = 1,768, aVE 23%, 95% CI 1%-40%) and patients aged >= 65 years (n = 1,407, aVE 20%, 95% CI -5% to 40%), but not in patients aged >= 75 years (n = 905, aVE 5%, 95% CI -37% to 35%). The aVE estimate in relation to PPV23/non-13-valent pneumococcal conjugate vaccine (PCV13) serotype pneumonia (n = 417 cases, 43.7% vaccinated) was 29% (95% CI 6%-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. Conclusions In the setting of an established national childhood PCV13 vaccination programme, PPV23 vaccination of clinical at-risk patient groups and adults aged >= 65 years provided moderate long-term protection against hospitalisation with PPV23 serotype pneumonia. These findings suggest that PPV23 vaccination may continue to have an important role in adult pneumococcal vaccine policy, including the possibility of revaccination of older adults.