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

Hannah Lawrence, Harry Pick, Vadsala Baskaran, Priya Daniel, Chamira Rodrigo, Deborah Ashton, Rochelle C. Edwards-Pritchard, Carmen Sheppard, Seyi D. Eletu, David Litt, Norman Fry, Samuel Rose, Caroline Trotter, Tricia M. McKeever, Wei Shen Lim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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) × 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.

Original languageEnglish
Article numbere1003326
JournalPLoS Medicine
Issue number10
Publication statusPublished - 23 Oct 2020

Bibliographical note

Funding Information:
This study is independent research funded in part by the University of Nottingham?s 2019-20 QR Strategic Priorities Fund and supported by the Nottingham National Institute for Health Research Biomedical Research Centre (NIHR BRC). The study concept was developed and agreed upon by the authors with no input from the funding bodies. The data are the sole responsibility of the authors, and the sponsor for the study was Nottingham University Hospitals NHS Trust. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, JCVI, or PHE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank Nick Andrews, Senior Statistician at Public Health England, for his support with statistics; the Nottingham Pneumonia Patient and Public Involvement group for their ongoing input in respiratory infection research; and all participants who gave their consent for the primary study.

Publisher Copyright:
© 2020 Lawrence et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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