The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada

Introduction: Annual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive. Aim: We investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults. Methods: We conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history. Results: We included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1-3 (26%; 95%CI: 13 to 37%), 4-6 (24%; 95%CI: 15 to 33%), 7-8 (13%; 95%CI: 2 to 22%), or 9-10 (7%; 95% CI: -4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously. Conclusions: Although VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.