Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19

Background: Waning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases. Aim: We examined the association between time since vaccination and laboratory -confirmed influenza to assess the change in influenza vaccine protection over time. Methods: Using linked laboratory and health administrative databases in Ontario, Canada, we identified community -dwelling individuals aged >= 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory -confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days. Results: There were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza -positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09 -times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04- 1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aOR(per 28 days) = 1.26; 95% CI: 0.97-1.64), whereas for per 28 days individuals aged >= 65 years, it was against influenza A(H3N2) (aOR(per 28 days) = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years. Conclusions: Influenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.