Objectives Growing evidence suggests that vaccines targeting respiratory pathogens have non-specific and broader effects. We aimed to investigate the non-specific effects of respiratory vaccines on acute lower respiratory infection (ALRI) hospitalisations and associated outcomes in children <5 years. We also assessed broader effects of respiratory vaccines, including antimicrobial prescribing patterns. Design Systematic review and meta-analysis. Data sources We searched online databases including Medline, Embase, CINAHL, Scopus and Clinical Trials.gov from inception to 24 January 2024. Eligibility criteria We included human studies involving non-specific/off-target effects of respiratory vaccines (including maternal, infant and childhood vaccines) and excluded studies investigating the Bacille Calmette-Guérin vaccine and non-pathogen-confirmed outcomes following pneumococcal conjugate vaccination (PCV). Data extraction and synthesis We used Research Screener, a machine learning tool, to semi-automate the abstract screening process and Covidence, a management and streamlining software for full-text reviews and data extraction. A meta-analysis was conducted if four or more studies reported on the same outcome and the same exposure vaccine. Results After removing duplicates, 9727 articles were identified. After screening and full-text reviews, 20 articles were eligible. Of those, four met the requirements for a meta-analysis which showed a 21% vaccine effectiveness (VE) (95% CI 8.0% to 32.0%) of maternal influenza vaccine against all-cause ALRI hospitalisations in infants <6 months (heterogeneity: 46.0%, p<0.01). Neutral and beneficial non-specific effects were mostly observed for respiratory vaccines against pathogen-confirmed hospitalisations, with the largest reduction observed in Spanish children fully vaccinated with PCV against influenza-confirmed hospitalisations (adjusted OR, aOR=0.52, 95% CI 0.24 to 0.99). Three articles on antibiotic prescribing rates reported reductions in vaccine recipients with VE up to 14.5% (95%CI 9.6% to 19.2%). Respiratory vaccines had discrepant results with broader outcomes of wheezing, all-cause acute otitis media and all-cause mortality associated with respiratory infection hospitalisation. Conclusions Our review demonstrated both protective and neutral non-specific effects of respiratory vaccines against ALRI-hospitalisations and related outcomes in young children. Such effects should be considered as part of the full value of a vaccine and how vaccine investments are prioritised. Further research on the impact of respiratory vaccines on antibiotic prescribing rates is essential as consistent reductions may help contribute to reducing the global burden of antimicrobial resistance. PROSPERO registration number CRD 42023476038.
Holland et al. (Mon,) studied this question.
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