Protection against influenza after annually repeated vaccination: a meta-analysis of serologic and field studies

Arch Intern Med. 1999 Jan 25;159(2):182-8. doi: 10.1001/archinte.159.2.182.


Background: According to common recommendations, influenza vaccination should be performed annually. It has been suggested that vaccination in previous years reduces vaccine efficacy in the long term.

Objective: To determine whether the protection of influenza vaccine decreases when vaccination is repeated annually.

Methods: Articles published between 1966 and 1997 were selected from MEDLINE. The end point for field studies was the influenza-related morbidity or mortality during influenza outbreaks (resulting in field protection rates). The end point for serologic studies was exceeding a protective postvaccination hemagglutination-inhibition titer (serologic protection rates). Protection rate differences between groups with single and multiple vaccinations were subjected to meta-analysis.

Results: Seven field studies (including 13 trials) supported the hypothesis that protection in multiple-vaccination groups is at least as good as that in single-vaccination groups. Ten trials with 5117 observations could be subjected to meta-analysis. The pooled protection-rate difference was close to 0 (1.1%; 95% confidence interval, -0.2% to 2.4%), thus detecting no difference between single or multiple vaccination. Twelve serologic studies (including 53 trials) showed heterogeneous results: 9 trials were significantly in favor of single vaccination, and 7 were in favor of multiple vaccination, but in most cases, there was no significant difference between the 2 vaccination groups. The pooled serologic protection-rate difference from 52 trials (12341 observations) was again close to 0 (1.7%; 95% confidence interval, -1.3% to 4.8%).

Conclusions: We did not detect any evidence for a decreasing protection with annually repeated influenza vaccination. Annual vaccination should not be discouraged in populations at risk.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood*
  • Clinical Trials as Topic
  • Disease Outbreaks
  • Humans
  • Immunization Schedule
  • Influenza Vaccines / administration & dosage*
  • Influenza, Human / epidemiology
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control*


  • Antibodies, Viral
  • Influenza Vaccines