Annual seasonal influenza vaccination is recommended for individuals at high risk of developing post-infection complications in many locations. However, reduced vaccine immunogenicity and effectiveness have been observed among repeat vaccinees in some influenza seasons. We investigated the impact of repeated influenza vaccination on relative vaccine effectiveness (VE) among individuals who were recommended for influenza vaccination in the United Kingdom with a retrospective cohort study using primary healthcare data from the Clinical Practice Research Datalink, a primary care database in the United Kingdom. Relative VE was estimated against general practitioner-diagnosed influenza-like illnesses (GP-ILI) and medically attended acute respiratory illnesses (MAARI) among participants who have been repeatedly vaccinated compared with first-time vaccinees using proportional hazards models. Relative VE against MAARI may be reduced for individuals above 65 years old who were vaccinated in the current and previous influenza seasons for some influenza seasons. However, these findings were not conclusive as we could not exclude the possibility of residual confounding in our dataset. The use of routinely collected data from electronic health records to examine the effects of repeated vaccination needs to be complemented with sufficient efforts to include negative control outcomes to rule out residual confounding.
