BACKGROUND: Concerns have been raised about intraseasonal waning of the protection conferred by influenza vaccination.

METHODS: During four influenza seasons, we consecutively recruited individuals aged 18years or older who had received seasonal influenza vaccine and were subsequently admitted to the hospital for influenza infection, asassessed by reverse transcription polymerase chain reaction. We estimated the adjusted odds ratio (aOR) of influenza infection by date of vaccination, defined by tertiles, as early, intermediate or late vaccination. We used a test-negative approach with early vaccination as reference to estimate the aOR of hospital admission with influenza among late vaccinees. We conducted sensitivity analyses by means of conditional logistic regression, Cox proportional hazards regression, and using days between vaccination and hospital admission rather than vaccination date.

RESULTS: Among 3615 admitted vaccinees, 822 (23%) were positive for influenza. We observed a lower risk of influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.68 (95% CI: 0.47-1.00) and 0.69 (95% CI: 0.50-0.95). We found no differences in the risk of admission with influenza among late versus early vaccinees in the 2012/2013A(H1N1)pdm09-dominant or 2013/2014B/Yamagata lineage-dominant seasons: aOR=1.18 (95% CI: 0.58-2.41) and 0.98 (95% CI: 0.56-1.72). When we restricted our analysis to individuals aged 65years or older, we found a statistically significant lower risk of admission with influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.61 (95% CI: 0.41-0.91) and 0.69 (95% CI: 0.49-0.96). We observed 39% (95% CI: 9-59%) and 31% (95% CI: 5-50%) waning of vaccine effectiveness among participants aged 65years or older during the two A(H3N2)-dominant seasons. Similar results were obtained in the sensitivity analyses.

CONCLUSION: Waning of vaccine protection was observed among individuals aged 65years old or over in two A(H3N2)-dominant influenza seasons.