Efficacy and effectiveness of high-dose versus standard-dose influenza vaccination for older adults: a systematic review and meta-analysis

Expert Rev Vaccines. 2018 May;17(5):435-443. doi: 10.1080/14760584.2018.1471989. Epub 2018 May 16.


Background: Influenza is responsible for a significant disease burden annually, especially in older adults. This study reviews the relative vaccine efficacy or effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared to standard-dose influenza vaccines (SD-IIV3) in adults ≥65 against influenza-associated outcomes to inform evidence-based decision-making to shift clinical practice and standard of care in this population.

Methods: A systematic review was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults ≥65. Results from individual seasons were meta-analyzed and a random-effects model was used to estimate pooled rVEs.

Results: After screening 992 studies, seven studies were meta-analyzed. HD-IIV3 demonstrated better protection against ILI compared to SD-IIV3 (rVE = 19.5%; 95% CI: 8.6-29.0%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 9.1%; 95% CI: 2.4-15.3%), as well as from influenza (rVE = 17.8%; 95% CI: 8.1-26.5%), pneumonia (rVE = 24.3%, 95% CI: 13.9-33.4%), and cardiorespiratory events (rVE = 18.2%; 95% CI: 6.8-28.1%). rVE against post-influenza mortality was 22.2% (95% CI: -18.2-48.8%) and 2.5% (95% CI: -5.2-9.5%) against all-cause mortality.

Conclusions: Available evidence suggests HD-IIV3 is more effective than SD-IIV3 at reducing the clinical outcomes associated with influenza infection in older adults and should be considered for routine use in the 65+ population.

Keywords: High dose influenza vaccine; death; effectiveness; efficacy; elderly; hospitalization; influenza; meta-analysis; seniors; systematic review.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Age Factors
  • Aged
  • Hospitalization / statistics & numerical data
  • Humans
  • Influenza Vaccines / administration & dosage*
  • Influenza, Human / epidemiology
  • Influenza, Human / mortality
  • Influenza, Human / prevention & control*
  • Pneumonia / epidemiology
  • Pneumonia / prevention & control
  • Seasons
  • Vaccination / methods*


  • Influenza Vaccines